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Tranexamic acid (TXA) effectively reduces blood loss and transfusion risk during total joint arthroplasty. Additionally, intraoperative irrigation with various antiseptic solutions is often utilized for the management and prevention of surgical site infection. However, interactions between various antiseptic solutions and TXA have not been investigated. The purpose of this in vitro study is to evaluate the stability of TXA in the presence of common orthopedic antiseptic solutions. Five antiseptic solutions-0.1% chlorhexidine (CHX) gluconate, 10% povidone-iodine (BTD), 0.5% sodium hypochlorite (Dakin's), 3% hydrogen peroxide (H

Bird's nest ferns (Asplenium spp.) support large numbers of invertebrates, including centipedes. As top invertebrate predators, centipedes drive ecosystem function, for example, by regulating decomposer populations, but we know little of their ecology in forest canopies. We provide the first detailed observations of the diversity and structure of the centipede communities of bird's nest ferns, revealing the importance of these epiphytes as nurseries for centipedes. We collected 305 centipedes equating to ˜11,300 mg of centipede biomass from 44 bird's nest ferns (22 of which were from the high canopy and 22 from the low canopy) in primary tropical rainforest in Sabah, Malaysian Borneo. Most abundant were the Scolopendromorpha (n = 227 individuals), followed by the Geophilomorpha (n = 59), Lithobiomorpha (n = 14), and Scutigeromorpha (n = 5). Although we observed very little overlap in species between the forest strata, scolopendromorph centipedes dominated throughout the canopy. Null model analysis revealed no significant competitive interactions; on the contrary, we observed centipedes sharing nest sites within the ferns on three of the ten occasions that we found nests. All nests belonged to centipedes of the family Scolopendridae, which are typically aggressive, and usually show negative spatial association. This study reveals a diverse community of canopy centipedes, providing further evidence of the importance of bird's nest ferns to a wide range of animals, many of which use the ferns at critical life stages. Future conservation strategies should regard these ubiquitous epiphytes as umbrella species and protect them accordingly in landscape management decisions.

Baited pitfall traps (BPTs) and flight intercept traps (FITs) are the most common methods employed for sampling dung beetle communities. These methods vary in their efficacy and are affected by factors such as the bait types used and the dispersal abilities of different dung beetle species. We present the first quantitative comparison of the community composition, taxonomic and functional diversity of dung beetles caught in human dung BPTs and FITs in Bornean tropical forests. Functional diversity metrics were calculated based on the three functional traits of nesting method, body length, and diel activity. We show that BPTs and FITs captured complementary communities with different functional traits, and that BPTs captured more functionally diverse communities. We therefore recommend using a combination of both BPTs and FITs for studies assessing the composition of dung beetles across habitat types. Our results also highlight that it is important to consider how trap type affects the trait composition of communities when relating dung beetle communities and functional traits to ecological functioning. We suggest modifications to FITs based on the design of harp traps to increase their effectiveness in capturing larger-bodied beetles. Accepted version EMS acknowledges funding from a British Ecological Society Small Ecological Project Grant, No.: 3256/ 4035, and the Varley-Gradwell Travelling Fellowship in Insect Ecology. EMS, DHB and VK were supported by a UK Natural Environment Research Council grant (NE/K016407/1). XRO was supported by the Nanyang President’s Graduate Scholarship.

OBJECTIVES To estimate the rate of and risk factors associated with cost-related medication nonadherence among older adults. DESIGN Cross-sectional analysis of the 2017 National Health Interview Survey (NHIS). SETTING Nationally representative health interview survey in the United States. PARTICIPANTS Survey respondents, aged 65 years or older (n = 5701 unweighted) in the 2017 wave of the NHIS. MEASUREMENTS Self-reported, cost-related medication nonadherence (due to cost: skip dose, reduce dose, or delay or not fill a prescription) and actions taken due to cost-related medication nonadherence (ask for lower-cost prescription, use alternative therapy, or buy medications from another country) were quantified. We used a series of multivariable logistic regression analyses to identify factors associated with cost-related medication nonadherence. We also reported analyses by chronic disease subgroups. RESULTS In 2017, 408 (6.8%) of 5901 older adults, representative of 2.7 million older adults nationally, reported cost-related medication nonadherence. Among those with cost-related medication nonadherence, 44.2% asked a physician for lower-cost medications, 11.5% used alternative therapies, and 5.3% bought prescription drugs outside the United States to save money. Correlates independently associated with a higher likelihood of cost-related medication nonadherence included: younger age, female sex, lower socioeconomic levels (eg, low income and uninsured), mental distress, functional limitations, multimorbidities, and obesity (P

Objective To explore the intrinsic role of inhibitor of DNA binding 1 (ID‐1) in rheumatoid arthritis (RA) fibroblast‐like synoviocytes (FLS) and to investigate whether ID‐1 is citrullinated and autoantigenic in RA. Methods RA patient serum ID‐1 levels were measured before and after infliximab treatment. RA FLS were transfected with a clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR‐associated protein 9 construct targeting ID‐1 to examine the effects of ID‐1 deletion. RA synovial fluid (SF) and homogenized synovial tissue (ST) were immunoprecipitated for ID‐1 and measured for citrullinated residues using an enzyme‐linked immunosorbent assay and Western blotting. Liquid chromatography tandem mass spectrometry (LC‐MS/MS) was performed on in vitro–citrullinated recombinant human ID‐1 (cit–ID‐1) to localize the sites of citrullination. Normal and RA sera and SF were analyzed by immunodot blotting for anti–citrullinated protein antibodies (ACPAs) to cit–ID‐1. Results RA patient serum ID‐1 levels positively correlated with several disease parameters and were reduced after infliximab treatment. RA FLS displayed reduced growth and a robust increase in interleukin‐6 (IL‐6) and IL‐8 production upon deletion of ID‐1. ID‐1 immunodepletion significantly reduced the levels of citrullinated residues in RA SF, and citrullinated ID‐1 was detected in homogenized RA ST (n = 5 samples; P < 0.05). Immunodot blot analyses revealed ACPAs to cit–ID‐1 but not to native ID‐1, in RA peripheral blood (PB) sera (n = 30 samples; P < 0.001) and SF (n = 18 samples; P < 0.05) but not in normal PB sera. Following analyses of LC‐MS/MS results for citrullination sites and corresponding reactivity in immunodot assays, we determined the critical arginines in ID‐1 for autoantigenicity: R33, R52, and R121. Conclusion Novel roles of ID‐1 in RA include regulation of FLS proliferation and cytokine secretion as well as autoantigenicity following citrullination.

Background Patients with microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) metastatic colorectal cancer (mCRC) show a significant response to checkpoint inhibitor therapies, but the economic impact of these therapies is unknown. A decision analytic model was used to explore the effectiveness and cost burden of MSI-H/dMMR mCRC treatment. Methods The treatment of hypothetical patients with MSI-H/dMMR mCRC was simulated in 2 treatment scenarios: a third-line treatment and an exploratory first-line treatment. The treatments compared were nivolumab, ipilimumab and nivolumab, trifluridine and tipiracil (third-line treatment), and mFOLFOX6 and cetuximab (first-line treatment). Disease progression, drug toxicity, and survival rates were based on the CheckMate 142, study of TAS-102 in patients with metastatic colorectal cancer refractory to standard chemotherapies (RECOURSE), and Cancer and Leukemia Group B/Southwest Oncology Group 80405 trials. The analyzed outcomes included survival (life-years), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). Results Ipilimumab with nivolumab was the most effective strategy (10.69 life-years and 9.25 QALYs for the third line; 10.69 life-years and 9.44 QALYs for the first line) in comparison with nivolumab (8.21 life-years and 6.76 QALYs for the third line; 8.21 life-years and 7.00 QALYs for the first line), trifluridine and tipiracil (0.74 life-years and 0.07 QALYs), and mFOLFOX6 and cetuximab (2.72 life-years and 1.63 QALYs). However, neither checkpoint inhibitor therapy was cost-effective in comparison with trifluridine and tipiracil (nivolumab ICER, $153,000; ipilimumab and nivolumab ICER, $162,700) or mFOLFOX6 and cetuximab (nivolumab ICER, $150,700; ipilimumab and nivolumab ICER, $158,700). Conclusions This modeling analysis found that both single and dual checkpoint blockade could be significantly more effective for MSI-H/dMMR mCRC than chemotherapy, but they were not cost-effective, largely because of drug costs. Decreases in drug pricing and/or the duration of maintenance nivolumab could make ipilimumab and nivolumab cost-effective. Prospective clinical trials should be performed to explore the optimal duration of maintenance nivolumab.

Logging and habitat conversion create hotter microclimates in tropical forest landscapes, representing a powerful form of localised anthropogenic climate change. It is widely believed that these emergent conditions are responsible for driving changes in communities of organisms found in modified tropical forests, although the empirical evidence base for this is lacking. Here we investigated how interactions between the physiological traits of genera and the environmental temperatures they experience lead to functional and compositional changes in communities of ants, a key organism in tropical forest ecosystems. We found that the abundance and activity of ant genera along a gradient of forest disturbance in Sabah, Malaysian Borneo, was defined by an interaction between their thermal tolerance (CTₘₐₓ) and environmental temperature. In more disturbed, warmer habitats, genera with high CTₘₐₓ had increased relative abundance and functional activity, and those with low CTₘₐₓ had decreased relative abundance and functional activity. This interaction determined abundance changes between primary and logged forest that differed in daily maximum temperature by a modest 1.1°C, and strengthened as the change in microclimate increased with disturbance. Between habitats that differed by 5.6°C (primary forest to oil palm) and 4.5°C (logged forest to oil palm), a 1°C difference in CTₘₐₓ among genera led to a 23% and 16% change in relative abundance, and a 22% and 17% difference in functional activity. CTₘₐₓ was negatively correlated with body size and trophic position, with ants becoming significantly smaller and less predatory as microclimate temperatures increased. Our results provide evidence to support the widely held, but never directly tested, assumption that physiological tolerances underpin the influence of disturbance‐induced microclimate change on the abundance and function of invertebrates in tropical landscapes. A free Plain Language Summary can be found within the Supporting Information of this article.

Light-induced manipulation techniques have been utilized to transport, trap, or levitate microscopic objects for a wide range of applications in biology, electronics, and photonics. Without making direct physical contact, they can provide simple yet powerful means for high-precision assembly of microscale functional blocks and components within the integrated circuit platforms, thereby offering a viable alternative to the conventional heterogeneous integration techniques, such as wafer/die bonding and transfer printing. Using a microbubble-based optofluidic pick-and-place assembly process, heterogeneous integration of compact III-V semiconductor photodetectors on a silicon-based photonic integrated circuit chip, enabling direct high-speed vertical electrical contacts for significantly improved photogenerated carrier transit distance/time, is experimentally demonstrated. The microdisk-shaped InGaAs p-i-n photodetector integrated on the silicon waveguide has a 3 dB bandwidth exceeding 50 GHz under the applied bias voltage of -1 V for near-infrared wavelengths around 1.55 mu m. The light-induced optofluidic assembly will provide a promising route for seamless heterogeneous integration of various optoelectronic components with high-speed and low-noise electrical interconnection on the fully processed silicon photonic/electronic integrated circuit platforms.

Importance This novel endpoint tracks functional vision changes in patients with inherited retinal dystrophies (IRDs) over time. Background The aims of the study were to determine whether a multi-luminance mobility test (MLMT) can detect functional vision changes over time in subjects with IRDs and to assess natural history and potential effects of investigational agents. Design This is a prospective, observational study. Participants Sixty-two subjects were enrolled. Sixty (29 normal sighted and 31 visually impaired) were eligible; 54 (28 visually impaired and 26 normal-sighted) completed all testing visits. Methods Subjects navigated MLMT courses three times over 1 year. At each visit, subjects completed testing using individual eyes, and both eyes, at up to nine standardized, increasing luminance levels (range 1 to 400 lux). Accuracy and speed were evaluated and compared with visual acuity (VA), visual field (VF) and a visual function questionnaire. Main Outcome Measures Accuracy and speed of normal and visually impaired subjects on MLMT, and reliability and content validity of MLMT were the main outcome measures. Results MLMT distinguished normal-sighted from visually impaired subjects. All control subjects passed all MLMT attempts at all tested light levels. Visually impaired subjects' performance varied widely; some declined over 1 year. Performance declined markedly below certain VA and VF thresholds. Concordance on performance on two baseline visits was high: correlations for accuracy were 94% and 98% for lowest common and highest common lux levels. Conclusions and Relevance MLMT differentiated visually impaired from control populations and, in visually impaired subjects, identified a range of performances; and tracked performance declines over time, consistent with these progressive conditions.

Objective: Rheumatoid arthritis (RA) causes destruction of the metacarpophalangeal (MCP) joints leading to hand deformities, pain, and loss of function. This study prospectively assessed long-term functional and health-related quality of life outcomes in RA patients with severe deformity at the MCP joints. Methods: RA patients between the ages of 18-80 with severe deformity at the MCP joints were referred to one of the three study sites. Subjects who elected to undergo silicone metacarpophalangeal joint arthroplasty (SMPA) while continuing with medical management were followed in the SMPA cohort. Subjects who elected to continue with medical management alone without surgery were followed in the non-SMPA cohort. Objective measurements included grip and pinch strength as well as arc of motion, ulnar drift, and extensor lag of the MCP joints. Patient reported outcomes included the Michigan Hand Questionnaire (MHQ) and the Arthritis Impact Measurement Scales questionnaire. Radiographs of SMPA implants were assessed and graded as intact, deformed, or fractured. Results: MHQ scores showed large improvements post-SMPA, and baseline-adjusted expected outcomes in the SMPA group were significantly better at year seven in function, aesthetics, satisfaction, and overall score compared to non-SMPA. SMPA subjects did not improve in grip or pinch strength, but achieved significant improvement and maintained the improvement long-term in ulnar drift and extensor lag. Conclusion: Benefits of the SMPA procedure are maintained over seven years with low rates of implant fracture or deformity. Non-SMPA patients remained stable in their hand function over the seven year study duration. This article is protected by copyright. All rights reserved.

An Artificial Intelligence system was developed and implemented for water, wastewater, and reuse plants to improve management of sensors, short and long-term maintenance plans, asset and investment management plans. It is based on an integrated approach to capture data from different computer systems and files. It adds a layer of intelligence to the data. It serves as a repository of key current and future operations and maintenance conditions that a plant needs have knowledge of. With this information, it can simulate the configuration of processes and assets for those conditions to improve or optimize operations, maintenance and asset management, using the IViewOps (Intelligent View of Operations) model. Based on the optimization through model runs, it is able to create output files that can feed data to other systems and inform the staff regarding optimal solutions to the conditions experienced or anticipated in the future. This article is protected by copyright. All rights reserved.

Objective The migration of health care toward a consumer-driven system favors increased patient participation during the treatment decision-making process. Patient involvement in treatment decision discussions has been linked to increased treatment adherence and patient satisfaction. Previous studies have quantified decision-making styles of patients with rheumatoid arthritis (RA); however, none of them have considered the evolution of patient involvement after living with RA for many years. We conducted a qualitative study to determine the decision-making model used by long-term RA patients, and to describe the changes in their involvement over time. Methods Twenty participants were recruited from the ongoing Silicone Arthroplasty in Rheumatoid Arthritis study. Semistructured interviews were conducted and data were analyzed using grounded theory methodology. Results Nineteen out of 20 participants recalled using the paternalistic decision-making (PDM) model immediately following their diagnosis. Fourteen of the 19 participants who initially used PDM evolved to shared decision-making (SDM). Participants attributed the change in involvement to the development of a trusting relationship with their physician, as well as to becoming educated about the disease. Conclusion When initially diagnosed with RA, patients may let their physician decide on the best treatment course. However, over time patients may evolve to exercise a more collaborative role. Physicians should understand that even within SDM, each patient can demonstrate a varied amount of autonomy. It is up to the physician to have a discussion with each patient to determine his or her desired level of involvement.

Individuals with diabetes mellitus are at an increased risk of developing a diabetic foot ulcer (DFU). This study evaluated the safety and efficacy of Integra Dermal Regeneration Template (IDRT) for the treatment of nonhealing DFUs. The Foot Ulcer New Dermal Replacement Study was a multicenter, randomized, controlled, parallel group clinical trial conducted under an Investigational Device Exemption. Thirty-two sites enrolled and randomized 307 subjects with at least one DFU. Consented patients were entered into the 14-day run-in phase where they were treated with the standard of care (0.9% sodium chloride gel) plus a secondary dressing and an offloading/protective device. Patients with less than 30% reepithelialization of the study ulcer after the run-in phase were randomized into the treatment phase. The subjects were randomized to the control treatment group (0.9% sodium chloride gel; n = 153) or the active treatment group (IDRT, n = 154). The treatment phase was 16 weeks or until confirmation of complete wound closure (100% reepithelialization of the wound surface), whichever occurred first. Following the treatment phase, all subjects were followed for 12 weeks. Complete DFU closure during the treatment phase was significantly greater with IDRT treatment (51%) than control treatment (32%; p = 0.001) at sixteen weeks. The median time to complete DFU closure was 43 days for IDRT subjects and 78 days for control subjects in wounds that healed. The rate of wound size reduction was 7.2% per week for IDRT subjects vs. 4.8% per week for control subjects (p = 0.012). For the treatment of chronic DFUs, IDRT treatment decreased the time to complete wound closure, increased the rate of wound closure, improved components of quality of life and had less adverse events compared with the standard of care treatment. IDRT could greatly enhance the treatment of nonhealing DFUs.

Recent evidence from several relatively small nested case-control studies in prospective cohorts shows an association between longer telomere length measured phenotypically in peripheral white blood cell (WBC) DNA and increased lung cancer risk. We sought to further explore this relationship by examining a panel of seven telomere-length associated genetic variants in a large study of 5,457 never-smoking female Asian lung cancer cases and 4,493 never-smoking female Asian controls using data from a previously reported genome-wide association study. Using a group of 1,536 individuals with phenotypically measured telomere length in WBCs in the prospective Shanghai Women's Health study, we demonstrated the utility of a genetic risk score (GRS) of seven telomere-length associated variants to predict telomere length in an Asian population. We then found that GRSs used as instrumental variables to predict longer telomere length were associated with increased lung cancer risk (OR = 1.51 (95% CI = 1.34-1.69) for upper vs. lower quartile of the weighted GRS, p value = 4.54 × 10(-14) ) even after removing rs2736100 (p value = 4.81 × 10(-3) ), a SNP in the TERT locus robustly associated with lung cancer risk in prior association studies. Stratified analyses suggested the effect of the telomere-associated GRS is strongest among younger individuals. We found no difference in GRS effect between adenocarcinoma and squamous cell subtypes. Our results indicate that a genetic background that favors longer telomere length may increase lung cancer risk, which is consistent with earlier prospective studies relating longer telomere length with increased lung cancer risk.

Objective Aminopeptidase N/CD13 (EC 3.4.11.2) is a metalloproteinase expressed by fibroblast-like synoviocytes (FLS). It has been suggested that CD13 can act chemotactically for T cells in rheumatoid arthritis (RA). We undertook this study to measure CD13 in vivo and in vitro in RA samples and to determine whether CD13 could play a role in the homing of T cells to the RA joint. Methods Interleukin-17–treated FLS were used to immunize mice, from which a novel anti-human CD13 monoclonal antibody (mAb), 591.1D7.34, was developed. The mAb 591.1D7.34 and a second anti-CD13 mAb, WM15, were used to develop a novel enzyme-linked immunosorbent assay (ELISA) for CD13, and CD13 enzymatic activity was measured in parallel. Chemotaxis of cytokine-activated T cells was measured by a chemotaxis-under-agarose assay. Results We detected substantial amounts of CD13 in synovial fluid (SF), sera, FLS lysates, and culture supernatants by ELISA, with a significant increase in CD13 in RA SF when compared to osteoarthritis SF. CD13 accounted for most but not all of the CD13-like enzymatic activity in SF. Recombinant human CD13 was chemotactic for cytokine-activated T cells through a G protein–coupled receptor and contributed to the chemotactic properties of SF independently of enzymatic activity. Conclusion CD13 is released from FLS into culture supernatants and is found in SF. CD13 induces chemotaxis of cytokine-activated T cells, a T cell population similar to that found in RA synovium. These data suggest that CD13 could play an important role as a T cell chemoattractant, in a positive feedback loop that contributes to RA synovitis.

Strong global demand for tropical timber and agricultural products has driven large-scale logging and subsequent conversion of tropical forests. Given that the majority of tropical landscapes have been or will likely be logged, the protection of biodiversity within tropical forests thus depends on whether species can persist in these economically exploited lands, and if species cannot persist, whether we can protect enough primary forest from logging and conversion. However, our knowledge of the impact of logging and conversion on biodiversity is limited to a few taxa, often sampled in different locations with complex land-use histories, hampering attempts to plan cost-effective conservation strategies and to draw conclusions across taxa. Spanning a land-use gradient of primary forest, once- and twice-logged forests, and oil palm plantations, we used traditional sampling and DNA metabarcoding to compile an extensive data set in Sabah, Malaysian Borneo for nine vertebrate and invertebrate taxa to quantify the biological impacts of logging and oil palm, develop cost-effective methods of protecting biodiversity, and examine whether there is congruence in response among taxa. Logged forests retained high species richness, including, on average, 70% of species found in primary forest. In contrast, conversion to oil palm dramatically reduces species richness, with significantly fewer primary-forest species than found on logged forest transects for seven taxa. Using a systematic conservation planning analysis, we show that efficient protection of primary-forest species is achieved with land portfolios that include a large proportion of logged-forest plots. Protecting logged forests is thus a cost-effective method of protecting an ecologically and taxonomically diverse range of species, particularly when conservation budgets are limited. Six indicator groups (birds, leaf-litter ants, beetles, aerial hymenopterans, flies, and true bugs) proved to be consistently good predictors of the response of the other taxa to logging and oil palm. Our results confidently establish the high conservation value of logged forests and the low value of oil palm. Cross-taxon congruence in responses to disturbance also suggests that the practice of focusing on key indicator taxa yields important information of general biodiversity in studies of logging and oil palm.

The intrasynovial flexor tendons of the hand are critical for normal hand function. Injury to these tendons can result in absent finger flexion, and a subsequent loss of overall hand function. The surgical techniques used to repair these tendons have improved in the past few decades, as have the postoperative rehabilitation protocols. In spite of these advances, intrasynovial flexor tendon repairs continue to be plagued by postoperative scar formation, which limits tendon gliding and prevents a full functional recovery. This paper describes the current challenges of flexor tendon repair, and evaluates the most recent advances and strategies for achieving an excellent functional outcome.

Aims Most patients with familial adenomatous polyposis (FAP) develop gastric fundic gland polyps, with many displaying low-grade dysplasia. This study evaluates the natural history and morphological phenotype of dysplasia in FAP-associated fundic gland polyps. Methods and results Patients with FAP and dysplastic fundic gland polyps (n = 24) were identified. Twenty-two of 24 FAP-associated dysplastic fundic gland polyps showed a gastric phenotype and two had mixed phenotype. During a mean 6.1-year follow-up (range 0.8–12.6 years) and 5.7 endoscopies (range 2–22), one patient (4%) was diagnosed with a fundic gland polyp with high-grade dysplasia, while 23 patients (96%) in this cohort had either no dysplasia or persistent low-grade dysplasia. Contemporary patients with sporadic fundic gland polyps with low-grade dyplasia had similar morphology and outcomes to the FAP-associated fundic gland polyp cohort. Dysplasia in fundic gland polyps (FAP-associated and sporadic) was associated less frequently with intestinal phenotype, high-grade dysplasia and the finding of concurrent or subsequent carcinoma compared to contemporary patients with sporadic gastric dysplasia not occurring in fundic gland polyps. Conclusions This cohort of patients with FAP-associated dysplastic fundic gland polyps rarely developed high-grade dysplasia and gastric adenocarcinoma was absent.

BACKGROUND Genome-wide association studies (GWAS) have identified that a ∼1 M region centromeric to the MYC oncogene on chromosome 8q24.21 harbors at least five independent loci associated with prostate cancer risk and additional loci associated with cancers of breast, colon, bladder, and chronic lymphocytic leukemia (CLL). Because GWAS identify genetic markers that may be indirectly associated with disease, fine-mapping based on sequence analysis provides important insights into patterns of linkage disequilibrium (LD) and is critical in defining the optimal variants to nominate for biological follow-up. METHODS To catalog variation in individuals of African ancestry, we resequenced a region (250 kb; chr8:128,050,768–128,300,801, hg19) containing several prostate cancer susceptibility loci as well as a locus associated with CLL. Our samples included 78 individuals from Ghana and 47 of African-Americans from Johns Hopkins University. RESULTS After quality control metrics were applied to next-generation sequence data, 1,838 SNPs were identified. Of these, 285 were novel and not yet reported in any public database. Using genotypes derived from sequencing, we refined the LD and recombination hotspots within the region and determined a set of tag SNPs to be used in future fine-mapping studies. Based on LD, we annotated putative risk loci and their surrogates using ENCODE data, which should help guide laboratory studies. CONCLUSIONS In comparison to the 1000 Genome Project data, we have identified additional variants that could be important in establishing priorities for future functional work designed to explain the biological basis of associations between SNPs and both prostate cancer and CLL. Prostate 74:579–589, 2014. © 2014 Wiley Periodicals, Inc.

The KRAS oncogene influences angiogenesis, metastasis and chemoresistance in colorectal cancers (CRCs), and these processes are all enhanced in hypoxic conditions. To define functional activities of mutant KRAS in a hypoxic microenvironment, we first performed cDNA microarray experiments in isogenic DKs5 and DKO3 colon cancer cell lines that differ only by their expression of mutant KRAS (K-ras(D13)). Adrenomedullin (ADM) was identified as one of the most significantly upregulated genes in DKs5 cells that express the KRAS oncogene in hypoxia (3.2-fold, p = 1.47 × 10(-5)). Ectopic expression of mutant KRAS (K-ras(V12)) in Caco-2 cells (K-ras(WT)) induced ADM, whereas selective knockdown of mutant KRAS alleles (K-ras(D13) or K-ras(V12)) in HCT116, DLD1 and SW480 colon cancer cells suppressed the expression of ADM in hypoxia. Knockdown of ADM in colon tumor xenografts blocked angiogenesis and stimulated apoptosis, resulting in tumor suppression. Furthermore, ADM also regulated colon cancer cell invasion in vitro. Among 56 patients with CRC, significantly higher expression levels of ADM were observed in samples harboring a KRAS mutation. Collectively, ADM is a new target of oncogenic KRAS in the setting of hypoxia. This observation suggests that therapeutic targets may differ depending upon the specific tumor microenvironment.

Forests in Southeast Asia are rapidly being logged and converted to oil palm. These changes in land-use are known to affect species diversity but consequences for the functional diversity of species assemblages are poorly understood. Environmental filtering of species with similar traits could lead to disproportionate reductions in trait diversity in degraded habitats. Here, we focus on dung beetles, which play a key role in ecosystem processes such as nutrient recycling and seed dispersal. We use morphological and behavioural traits to calculate a variety of functional diversity measures across a gradient of disturbance from primary forest through intensively logged forest to oil palm. Logging caused significant shifts in community composition but had very little effect on functional diversity, even after a repeated timber harvest. These data provide evidence for functional redundancy of dung beetles within primary forest and emphasize the high value of logged forests as refugia for biodiversity. In contrast, conversion of forest to oil palm greatly reduced taxonomic and functional diversity, with a marked decrease in the abundance of nocturnal foragers, a higher proportion of species with small body sizes and the complete loss of telecoprid species (dung-rollers), all indicating a decrease in the functional capacity of dung beetles within plantations. These changes also highlight the vulnerability of community functioning within logged forests in the event of further environmental degradation.

To test the potential stimulatory effect of local application of periodontal ligament (PDL) stromal cells on soft tissue regeneration.Fluorescently labeled PDL cells outgrown from extracted human premolars or phosphate-buffered saline were locally injected to the cutaneous wounds created on mice. Soft tissue regeneration was evaluated for 14 days using photographs and histomorphometry. PDL cell engraftment was tracked with confocal microscopy. To detect the paracrine effect of the PDL cells on soft tissue regeneration, PDL cell-conditioned medium (CM) was evaluated for the concentration of secretory factors, transforming growth factor-beta 1 (TGFβ1). The effect of PDL CM on the proliferation and migration of dermal fibroblast and keratinocyte was tested using MTT assay and migration assay.The application of PDL cells significantly promoted soft tissue regeneration compared with the application of PBS. Self-replicating PDL cells were engrafted into the hair follicles of the host tissue. Dermal fibroblast proliferation and keratinocyte migration were significantly enhanced by the treatment with PDL CM. Physiologically significant amount of TGFβ1 was secreted from PDL cells into the CM.Local injection of PDL cells promoted soft tissue regeneration in part by the enhancement of fibroblast proliferation and keratinocyte migration through a paracrine mechanism.

Stem rot of Anoectochilus formosanus (Af) caused by Fusarium oxysporum (Fo) is a major limiting factor to jewel orchid production in Taiwan. Fo causes discoloration in vascular tissues. However, some newly collected Fo isolates from Af stem rot do not cause vascular discoloration, suggesting changes may have occurred in the pathogen. Among recent Fo isolates from Af there are two colony types, the cottony alba (CA) and the sporodochial (S). In order to confirm that both colony types cause Af stem rot, 200 isolates were obtained from diseased stems in Nantou County and characterized by colony type and whether or not the infected plants had vascular discoloration. Isolates of both the CA and S types caused stem rot of Af; some isolates in each colony type caused vascular discoloration whilst others did not. Pathogenicity tests with 22 isolates resulted in stem rot disease severity ratings on Af of 3·1–4·0 and 2·1–4·0 with CA and S type colonies, respectively. The same isolates failed to cause disease on Cattleya, Dendrobium or Phalaenopsis plants. Phylogenetic analysis of partial intergenic spacer sequences showed that these isolates were distinguishable from other formae speciales of Fo and could be separated into two groups correlated with the CA or S type colonies with high bootstrap. Based on pathogenic, morphological and molecular characterizations, the Fo that causes stem rot of Af is proposed to be a new forma specialis, F. oxysporum f. sp. anoectochili, with different pathotypes.

Introduction We previously conducted a randomized trial comparing the endo-laparoscopic approach (i.e. placing self-expanding metallic stents followed by laparoscopic resection) and conventional open surgery in the treatment of obstructing left-sided colon cancer. This study is a follow-up of the previous randomized trial and aims to report the long-term outcomes of the two groups. Methods Forty-eight patients from the randomized trial were followed up in an outpatient clinic with regular monitoring. Patients were compared for clinicopathological variables, disease recurrence and survival rates. Results Clinicopathological details were comparable between the two groups. During the median follow-up periods of 32 months for the open group and 65 months endo-laparoscopic group, no statistically significant difference was observed between the groups in disease recurrence rate, 5-year overall survival (27% vs 48%, P = 0.076) and 5-year disease-free survival rates (48% vs 52%, P = 0.63). Conclusion Besides being a safe bridge to subsequent elective laparoscopic surgery, preoperative self-expanding metallic stents insertion does not adversely affect oncological outcomes and patient survival. Based on our data, the endo-laparoscopic approach is the treatment of choice for patients presenting with malignant left-sided colonic obstruction.

Aim Laparoscopic colectomy for colorectal cancer is associated with definite short-term benefits, and is increasingly practised worldwide. The limitations of a pure laparoscopic approach include a relative lack of tactile feedback and long procedural time. Hand-assisted laparoscopic surgery was introduced in an attempt to facilitate operation by improving the tactile sensation. To date, there is no consensus as to which approach is better. Herein we conducted a randomized controlled trial comparing hand-assisted laparoscopic colectomy (HALC) with total laparoscopic colectomy (TLC) in the management of right-sided colonic cancer. Methods Adult patients with carcinoma of the caecum and ascending colon were recruited and randomized to undergo either HALC or TLC. Measured outcomes included operative time, blood loss, conversion rate, postoperative morbidities, postoperative pain, length of hospital stay, disease recurrence and patient survival. Results Sixty patients (HALC = 30, TLC = 30) were recruited. The two groups were comparable with regard to age, gender distribution, body mass index and final histopathological staging. No difference was observed between the groups in terms of operating time, conversion rate, operative blood loss, pain score and length of hospital stay. With a median follow-up of 27 to 33 months, no difference was observed in terms of disease recurrence, and the 5-year survival rates remained similar (83%vs 80%, P = 0.923). Conclusion HALC is safe and feasible, but it does not show any significant benefits over TLC in terms of operating time and conversion rate. Routine use of the hand-assisted laparoscopic technique in right hemicolectomy is therefore not recommended.

Introduction: Spinal cord decompression sickness (DCS) is a rare condition that can lead to spinal cord infarction. Despite the low incidence of diving-related DCS, we have managed to collect the data and MRI findings of seven patients who have been diagnosed with and treated for DCS in our local hyperbaric facility. This study describes the clinical presentation, MRI spinal cord findings, treatment administered and outcome of these patients. Methods: The patient medical records, from 1997 to 2007, were retrospectively reviewed. All patients with a final diagnosis of DCS and who underwent examination were included. The images were independently reviewed by two radiologists who recorded the location and number of lesions within the spinal cord. The Frankel grading was used to assess the initial and clinical outcome response. Results: Patchy-increased T2W changes affecting several levels at the same time were found. Contrary to the popular notion that venous infarction is the leading cause of DCS, most of our patients also demonstrated affliction of grey matter, which is typically seen in an arterial pattern of infarction. Initial involvement of multiple (>6) spinal cord levels was associated with a poor outcome. Patients who continued to have multiple neurological sequelae with less than 50% resolution of symptoms despite recompression treatment were also those who had onset of symptoms within 30 min of resurfacing. Conclusions: DCS is probably a combination of both arterial and venous infarction. Short latency to the onset of neurological symptoms and multilevel cord involvement may be associated with a poorer outcome.

Aim Instrument crowding is encountered in single-incision laparoscopic surgery (SILS). Our aim was to compare the results of SILS with those of conventional laparoscopic surgery (CLS) for malignant colorectal disease. Methods The records of 27 patients who received SILS for the treatment of malignant disease using a home-made multiple-port system were compared with those of 68 patients who received CLS performed in a standard manner using four to five trocar sites. Results There were no significant differences in age, gender, disease stage, tumour location or tumour size between the SILS and CLS groups. The most common surgery was high anterior resection in both groups (SILS, 63.0%vs CLS, 58.8%). There were no significant differences between the groups in types of surgery performed, length of bowel resected, resection margin, blood loss, duration of surgery or postoperative complications. Postoperative pain scores were significantly higher in the SILS group than in the CLS group (3.07 ± 1.14 vs 2.41 ± 0.63, respectively, P

Short-term benefits of laparoscopic colectomy for colonic cancer have been proved in different clinical trials [1–3]; patients will benefit from less postoperative pain, reduced pain-related and wound-related complications, as well as faster return of bowel function. However, abdominal incisions for retrieval of specimen are associated with increased postoperative pain and sometimes wound-related complications, compromising the benefits of minimally invasive surgery.

Aim Laparoscopic surgery for locally advanced tumours with extramural involvement is still controversial. It is believed that laparoscopic excision of T4 cancers is technically difficult and may result in prolonged operative time, increased conversion rate, added postoperative morbidity, and suboptimal oncological clearance. Method Our unit has been practising laparoscopic colorectal surgery since 1992, and all data are entered into a database prospectively. Since 1999 we have routinely used the laparoscopic approach for colorectal cancer resections. Data regardingpatients with a histologically T4 cancer operated on between 1999 and 2008 were analysed. Outcomes included operating time, conversion rate, postoperative complications and oncological outcome. Results Over a 10-year period, 146 patients (male 75) with a T4 cancer underwent laparoscopic resection. The median operating time was 125 (range, 46–285) min and the median blood loss was 50 (0–1800) ml. The conversion rate was 16%. Six (4.1%) patients experienced anastomotic leakage. The median number of lymph nodes harvested was 13 (2–40). One hundred and two (70%) patients underwent curative resection. The recurrence rates were 41% and 53% for stage II and III patients, respectively. Four (3.9%) patients had local recurrence. At a median follow up of 18 (1–118) months, the overall survival was 25 months, with median overall survival for patients with stage II, III and IV disease being 63, 36 and 12 months, respectively. Conclusion Laparoscopic colectomy in histologically T4 cancer is safe. Oncological outcomes remain satisfactory. Based on our data, provided expertise is available, patients with locally advanced tumours should not be excluded from a laparoscopic approach.

Organisms associated with another species may experience both costs and benefits from their partner. One of these costs is competition, which is the more likely if the two species are ecologically similar. Parabioses are associations between two ant species that share a nest and often attend the same food sources. Albeit parabioses are probably mutualistic, parabiotic partners may compete for food. We therefore investigated feeding niches and dietary overlap of two parabiotically associated ants in Borneo using cafeteria experiments and stable isotope analyses. The two species strongly differed in their food choices. While Crematogaster modiglianii mostly foraged at carbohydrate-rich baits, Camponotus rufifemur preferred urea-rich sources. Both species also consumed animal protein. The 15 N concentration in Ca. rufifemur workers was consistently lower than in Cr. modiglianii. Camponotus rufifemur but not Cr. modiglianii possesses microbial endosymbionts, which can metabolize urea and synthesize essential amino acids. Its lower 15 N signature may result from a relatively higher intake of plant-based or otherwise 15 N-depleted nitrogen. Isotopic signatures of the two partners in the same parabiosis showed strongly parallel variation across nests. As we did not find evidence for spatial autocorrelation, this correlation suggests an overlap of food sources between the two ant species. Based on model simulations, we estimated a diet overlap of 22-66% for nitrogen sources and 45-74% for carbon sources. The overlap may arise from either joint exploitation of the same food sources or trophallactic exchange of food. This suggests an intense trophic interaction and potential for competition between the parabiotic partners.

BACKGROUND Genome-wide association studies of prostate cancer have identified single nucleotide polymorphism (SNP) markers in a region of chromosome 11q13.3 in men of European decent. A fine-mapping analysis with tag SNPs in the cancer genetic markers of susceptibility study identified three independent loci, marked by rs10896438, rs12793759, and rs10896449. This study further annotates common and uncommon variation across this region. METHODS A next generation resequence analysis of a 122.9-kb region of 11q13.3 (68,642,755-68,765,690) was conducted in 78 unrelated individuals of European background, 1 CEPH trio, and 1 YRI trio. RESULTS In total, 644 polymorphic loci were identified by our sequence analysis. Of these, 166 variants—118 SNPs and 48 insertion-deletion polymorphisms (indels)—were novel, namely not present in the 1000 Genomes or International HapMap Projects. We identified 22, 25, 6, and 4 variants strongly correlated (r2 ≥ 0.8) with rs10896438, rs10896449, rs12793759, and rs11228565, respectively. HapMap SNPs were in linkage disequilibrium (r2 ≥ 0.8) with 48%, 69%, 14%, and 60% of SNPs marking bins by rs10896438, rs10896449, rs12793759, and rs11228565, respectively. CONCLUSIONS Our next generation resequence analysis compliments publicly available datasets of European descent (HapMap, build 28 and 1000 Genome, Pilot 1, October 2010), underscoring the value of targeted resequence analysis prior to initiating functional studies based on public databases alone. Increasing the number of common variants enables investigators to better prioritize variants for functional studies designed to uncover the biological basis of the direct association(s) in the region. Prostate 72:476–486, 2012. © 2011 Wiley Periodicals, Inc.

Background Older adults with questionable dementia are at risk of progressing to dementia, and early intervention is considered important. The present study investigated the effectiveness of a virtual reality (VR)-based memory training for older adults with questionable dementia. Methods A pre-test and post-test design was adopted. Twenty and 24 older adults with questionable dementia were randomly assigned to a VR-based and a therapist-led memory training group, respectively. Primary outcome measures included the Multifactorial Memory Questionnaire and Fuld Object Memory Evaluation. Results Both groups demonstrated positive training effects, with the VR group showing greater improvement in objective memory performance and the non-VR group showing better subjective memory subtest results in the Multifactorial Memory Questionnaire. Conclusion The use of VR seems to be acceptable for older adults with questionable dementia. Further study on the effect of educational background and memory training modality (visual, auditory) is warranted. Copyright © 2011 John Wiley & Sons, Ltd.

The pathogenicity of 35 Fusarium solani isolates obtained from diseased leaves of greenhouse-grown Phalaenopsis plants in Taiwan was tested on different orchids, including Phalaenopsis sp., Cymbidium spp., Oncidium sp., Dendrobium sp. and Cattleya sp., plus pea (Pisum sativum), chrysanthemum (Chrysanthemum indicum) and cucurbit [melon (Cucumis melo) and cucmber (C. sativus)] plants. Isolates of F. solani from Phalaenopsis spp. caused severe leaf yellowing on Phalaenopsis and mild symptoms on Cymbidium spp., but no visual symptoms on Oncidium sp., Dendrobium sp., Cattleya sp., pea, chrysanthemum or melon. Fusarium solani isolates collected from Phalaenopsis, pea and cucurbits were molecularly characterized by internal transcribed spacer (ITS), intergenic spacer (IGS) and β-tubulin gene analyses. Phylogenetic trees constructed by distance and parsimony methods indicated that isolates from Phalaenopsis were grouped into one type based on ITS, IGS and β-tubulin sequences with high bootstrap value (> 84%) support, compared to ‘formae speciales’ of F. solani from the other hosts. These analyses show that isolates of F. solani from Phalaenopsis are distinct from F. solani isolates from other hosts in Taiwan. Therefore, it is proposed that F. solani isolates that incite Phalaenopsis leaf yellowing be designated F. solani f. sp. phalaenopsis.

Critical to the infrastructure of a strong academic medical center is the medical faculty. Attention to job satisfaction of academic medical faculty has gained national attention in part due to the current economic climate in which recruitment of faculty to replace those who leave is costly. Recent national survey data from the American Association of Medical Colleges (AAMC) reported a staggering 38–40% attrition rate of academic medical faculty over a ten year period.1 Because faculty retention and job satisfaction are intimately linked, understanding what drives and satisfies academic medical faculty is invaluable for providing continuos and quality patient care,2 teaching the next generation of physicians, and minimizing the high cost of recruiting new faculty.3, 4 Despite being a relatively new track, the number of clinical track faculty is currently nearly comparable with the instructional track, which emphasizes the traditional tripartite missions of patient care, research and teaching.5 By contrast, the clinical track’s primary missions are in patient care and teaching (Figure 1A). This striking increase in the non-tenure clinical track faculty reflects a national trend6 and makes retention of faculty in the clinical track equally important to retention in the instructional track, so that an academic medical center can meet its responsibilities to its patients and maintain financial stability. Figure 1 Conceptual Framework for Comparing Instructional and Clinical Track Faculty Job Satisfaction Because the clinical track is structurally different from the instructional track, we sought to identify and contrast predictors of job satisfaction between the two tracks by conducting a medical school faculty survey. We designed a conceptual framework7 to illustrate the overlapping yet distinct roles of an academic faculty member, representing the track’s primary responsibilities (Figure 1A) and categorized overlapping individual, departmental and institutional characteristics previously described in the literature as influencing faculty job satisfaction (Figure 1B). Academic medical faculty surveys have been used to examine differences in job satisfaction among clinical track faculty,8 to investigate gender differences,9, 10 or all academic medical faculty,11–14 and have suggested that job satisfaction is largely related to autonomy,13 work-life balance,10, 15 departmental leadership,11 salary compensation,11, 13 and having a mentor.16, 17 Our conceptual framework is structured to reflect these findings from these previous studies, which describe characteristics that can be derived from varying hierarchical levels as well as literature supporting a strong association between job satisfaction with faculty retention.11 To our knowledge, no prior study has directly compared predictors of job satisfaction between the two faculty tracks despite the differing primary missions. We formulated the following hypotheses: (1) similar areas of job satisfaction will emerge for both faculty tracks due to overlapping missions of teaching and patient care, and (2) because of the different expectations of the instructional and clinical faculty tracks, predictors of job satisfaction will vary and different strategies will need to be proposed for each faculty track to enhance faculty satisfaction.

Oral Diseases (2011) 17, 187–193 Objectives: To investigate the level and interrelationship of nerve growth factor (NGF) and sensory neuropeptides [substance P (SP), calcitonin gene-related peptide (CGRP)] in plasma and saliva of chronic migraine patients, and to analyze the association between pain intensity and their concentration. Materials and methods: Plasma and resting whole saliva were collected from 33 chronic migraine patients and 36 control subjects. NGF, SP, and CGRP concentrations were measured by enzyme immunoassay and pain intensity of each subject was measured using the Graded Chronic Pain Scale. Results: Chronic migraine patients showed higher NGF and neuropeptide levels in both plasma and saliva compared to the control subjects. Plasma NGF, and plasma and saliva levels of SP and CGRP were highly associated with pain intensity. There was a significant positive correlation between NGF and both neuropeptide levels in plasma, and between the neuropeptide levels in both plasma and saliva. Plasma levels of SP and CGRP were significantly correlated with their saliva level. Conclusions: The increased production of NGF and sensory neuropeptides may play an important role in the maintenance of pain in chronic migraine and analysis results of human saliva could act as an index of disease state and therapeutic outcome.

BACKGROUND: Several publications reporting on health disparities document that ethnic minorities disproportionately experience delays in healthcare access, delivery, and treatment. However, few studies examine factors underlying access and receipt of healthcare among cancer survivors from the patient perspective. This study explores diagnostic and therapeutic care delays among a multiethnic sample of breast and cervical cancer survivors and examines contextual factors influencing diagnostic and therapeutic care delays. METHODS: Population-based sampling and a cross-sectional design were used to recruit 1377 survivors (breast cancer, n = 698; cervical cancer, n = 679). This multiethnic sample included 449 European American, 185 African American, 468 Latina American, and 275 Asian American survivors. RESULTS: Latina Americans were more likely to report diagnostic delays (P = .003), whereas African Americans were more likely to report therapeutic delays (P = .007). In terms of cancer type, cervical cancer survivors were more likely to report diagnostic (P = .004) and therapeutic delays (P = .000) compared with breast cancer survivors. “Fear of finding cancer” was the most frequently cited reason for diagnostic delays, and “medical reasons” were most frequently cited for therapeutic delays. CONCLUSIONS: Due in part to a higher proportion of diagnostic and therapeutic delays, ethnic minorities endure greater cancer burden, including poorer survival and survivorship outcomes. The medical community must recognize the impact of existing psychological and cultural dimensions on diagnostic care, as well as the personal and healthcare system level barriers that contribute to therapeutic delays. Cancer 2010. © 2010 American Cancer Society.

Objective To evaluate a case management (CM) model for people with mild dementia, whereby resources within the family and in the community were mobilized and optimally used. Method Community dwelling psychiatric and geriatrics outpatients with mild dementia were randomized to receive CM by a trained occupational therapist for 4 months (CM group, N = 59) or usual care only (control group, N = 43). Primary outcome indicators included the Zarit Burden Scale (ZBI), General Health Questionnaire (GHQ), and Personal Well-Being Index for Adult (PWI-A) of the family caregivers. Secondary outcome indicators included the Mini-Mental State Examination (MMSE), Neuropsychiatric Inventory (NPI), Cornell Scale for Depression in Dementia (CSDD), and Personal Well-Being Index for Intellectually Disabled (PWI-ID) of the demented subjects as measured at fourth and twelfth months. Result CSDDis reduced in the CM group at fourth month, but not at twelfth month. The changes in outcome variables of persons with dementia did not differ between the groups (Mann–Whitney U-test, p > 0.05). At follow-up, CM group used more day care and domestic helpers than control group (χ2, p > 0.05). Conclusion Case management for Chinese persons with mild dementia outpatients did not show significant effects in reducing caregiver burden, but encouraged family caregivers to seek external support. Copyright © 2009 John Wiley & Sons, Ltd.

Aim Total mesorectal excision (TME) is currently the gold standard for resection of mid or low rectal cancer and is associated with a low local recurrence rate. However, few studies have reported the long-term oncological outcome following use of a laparoscopic approach. The aim of this study was to evaluate the long-term oncological outcome after laparoscopic sphincter-preserving TME with a median follow up of about 4 years. Method Patients with mid or low rectal cancer who underwent laparoscopic sphincter-preserving TME with curative intent between March 1999 and March 2009 were prospectively recruited for analysis. Results During the 10-year study period, 177 patients underwent laparoscopic sphincter-preserving TME with curative intent for rectal cancer. Conversion was required in two (1%) patients. There was no operative mortality. At a median follow-up period of 49 months, local recurrence had occurred in nine (5.1%) patients. The overall metastatic recurrence rate after curative resection was 22%. The overall 5-year survival and 5-year disease-free survival in the present study were 74% and 71%, respectively. Conclusion The results of this study show that laparoscopic sphincter-preserving TME is safe with long-term oncological outcomes comparable to those of open surgery.

The limitations of the current state of the art Ni-YSZ cermet anodes with respect to Redox stability, coking and sulphur tolerance are well acknowledged. A material which mitigates all or even some of these issues would be of great importence for the continued development of robust SOFC systems. One such promising material system is based around the perovskite (La,Sr)Cr0.5Mn0.5O3 (LSCM). In this paper, some aspects of the work, carried out to integrate LSCM anodes into the IP-SOFC, are described. The intricacies of the introduction of a new material into an existing stack design concept are considered and how this impacts the performance and requirements of adjacent materials. In the case of the LSCM integration, at least as much work has gone into the development of these layers as into the anode itself. In particular, the design of a current collector to optimise both the conductivity across the layers and the adhesion to the anode has proved to be a challenging task within the normal design constraints of the IP-SOFC. Initial perfomance of around 75 mW cm–2 in a stack repeat unit test is encouraging and initial analysis has suggested that further development of the current collecting microstructure will confer significant performance improvements.