Malentangled: Function Redacting Tape

The neologism entanglement proposes that all things are connected through super-complex meshworks of mutable interdependencies. This entanglement of interdependencies is often obscured through forgetness, a radically reductive process by which things are taken to be isolated and interdependencies are forgotten. In some instances – for example when objects break – people are again reminded of the interdependentness of things. Malentanglement theory proposes that forgetness may also encounter a remindness through humour, and not only through catastrophe (depunctualisation). The ‘Function Redacting Tape’ project takes redaction as a method for doctoring documents, but it deploys this method in the material context of design. Project Participants are provided with black PVC adhesive tape and invited to consider the functions of designed objects. They are then asked to redact these functions (using the tape) and in doing so to make documented interventions that draw back the metaphorical veil of forgetness for reasons of design enquiry. The project functions as a sort of rudimentary cultural probe that might shed some light on entanglement, humour, and design, whilst simultaneously testing the employment of humour to aid participation in design research

Lessons to be learned by comparing integrated fisheries stock assessment models (SAMs) with integrated population models (IPMs)

AEP was partially funded by the Cooperative Institute for Climate, Ocean, & Ecosystem Studies (CICOES) under NOAA Cooperative Agreement NA15OAR4320063, Contribution No. 2023-1331.Integrated fisheries stock assessment models (SAMs) and integrated population models (IPMs) are used in biological and ecological systems to estimate abundance and demographic rates. The approaches are fundamentally very similar, but historically have been considered as separate endeavors, resulting in a loss of shared vision, practice and progress. We review the two approaches to identify similarities and differences, with a view to identifying key lessons that would benefit more generally the overarching topic of population ecology. We present a case study for each of SAM (snapper from the west coast of New Zealand) and IPM (woodchat shrikes from Germany) to highlight differences and similarities. The key differences between SAMs and IPMs appear to be the objectives and parameter estimates required to meet these objectives, the size and spatial scale of the populations, and the differing availability of various types of data. In addition, up to now, typical SAMs have been applied in aquatic habitats, while most IPMs stem from terrestrial habitats. SAMs generally aim to assess the level of sustainable exploitation of fish populations, so absolute abundance or biomass must be estimated, although some estimate only relative trends. Relative abundance is often sufficient to understand population dynamics and inform conservation actions, which is the main objective of IPMs. IPMs are often applied to small populations of conservation concern, where demographic uncertainty can be important, which is more conveniently implemented using Bayesian approaches. IPMs are typically applied at small to moderate spatial scales (1 to 104 km2), with the possibility of collecting detailed longitudinal individual data, whereas SAMs are typically applied to large, economically valuable fish stocks at very large spatial scales (104 to 106 km2) with limited possibility of collecting detailed individual data. There is a sense in which a SAM is more data- (or information-) hungry than an IPM because of its goal to estimate absolute biomass or abundance, and data at the individual level to inform demographic rates are more difficult to obtain in the (often marine) systems where most SAMs are applied. SAMs therefore require more 'tuning' or assumptions than IPMs, where the 'data speak for themselves', and consequently techniques such as data weighting and model evaluation are more nuanced for SAMs than for IPMs. SAMs would benefit from being fit to more disaggregated data to quantify spatial and individual variation and allow richer inference on demographic processes. IPMs would benefit from more attempts to estimate absolute abundance, for example by using unconditional models for capture-recapture data.Publisher PDFPeer reviewe

Use of Fatty Acid Analysis to Determine Dispersal of Caspian Terns in the Columbia River Basin, U.S.A.

Lethal control, which has been used to reduce local abundances of animals in conflict with humans or with endangered species, may not achieve management goals if animal movement is not considered. In populations with emigration and immigration, lethal control may induce compensatory immigration, if the source of attraction remains unchanged. Within the Columbia River Basin (Washington, U.S.A.), avian predators forage at dams because dams tend to reduce rates of emigration of juvenile salmonids (Oncorhynchus spp.), artificially concentrating these prey. We used differences in fatty acid profiles between Caspian Terns (Hydroprogne caspia) at coastal and inland breeding colonies and terns culled by a lethal control program at a mid-Columbia River dam to infer dispersal patterns. We modeled the rate of loss of fatty acid biomarkers, which are fatty acids that can be traced to a single prey species or groups of species, to infer whether and when terns foraging at dams had emigrated from the coast. Nonmetric multidimensional scaling showed that coastal terns had high levels of C20 and C22 monounsaturated fatty acids, whereas fatty acids of inland breeders were high in C18:3n3, C20:4n6, and C22:5n3. Models of the rate of loss of fatty acid showed that approximately 60% of the terns collected at Rock Island Dam were unlikely to have bred successfully at local (inland) sites, suggesting that terns foraging at dams come from an extensive area. Fatty acid biomarkers may provide accurate information about patterns of dispersal in animal populations and may be extremely valuable in cases where populations differ demonstrably in prey base

Short-Term Outcomes of Secondary Liver Surgery for Initially Unresectable Colorectal Liver Metastases following Modern Induction Systemic Therapy in the Dutch CAIRO5 Trial

Objective: To present short-term outcomes of liver surgery in patients with initially unresectable colorectal liver metastases (CRLM) downsized by chemotherapy plus targeted agents. Background: The increase of complex hepatic resections of CRLM, technical innovations pushing boundaries of respectability, and use of intensified induction systemic regimens warrant for safety data in a homogeneous multicenter prospective cohort. Methods: Patients with initially unresectable CRLM, who underwent complete resection after induction systemic regimens with doublet or triplet chemotherapy, both plus targeted therapy, were selected from the ongoing phase III CAIRO5 study (NCT02162563). Short-term outcomes and risk factors for severe postoperative morbidity (Clavien Dindo grade ≥ 3) were analyzed using logistic regression analysis. Results: A total of 173 patients underwent resection of CRLM after induction systemic therapy. The median number of metastases was 9 and 161 (93%) patients had bilobar disease. Thirty-six (20.8%) 2-stage resections and 88 (51%) major resections (>3 liver segments) were performed. Severe postoperative morbidity and 90-day mortality was 15.6% and 2.9%, respectively. After multivariable analysis, blood transfusion (odds ratio [OR] 2.9 [95% confidence interval (CI) 1.1-6.4], P = 0.03), major resection (OR 2.9 [95% CI 1.1-7.5], P = 0.03), and triplet chemotherapy (OR 2.6 [95% CI 1.1-7.5], P = 0.03) were independently correlated with severe postoperative complications. No association was found between number of cycles of systemic therapy and severe complications (r = -0.038, P = 0.31). Conclusion: In patients with initially unresectable CRLM undergoing modern induction systemic therapy and extensive liver surgery, severe postoperative morbidity and 90-day mortality were 15.6% and 2.7%, respectively. Triplet chemotherapy, blood transfusion, and major resections were associated with severe postoperative morbidity

The soil-borne white root rot pathogen Rosellinia necatrix expresses antimicrobial proteins during host colonization

Rosellinia necatrix is a prevalent soil-borne plant-pathogenic fungus that is the causal agent of white root rot disease in a broad range of host plants. The limited availability of genomic resources for R. necatrix has complicated a thorough understanding of its infection biology. Here, we sequenced nine R. necatrix strains with Oxford Nanopore sequencing technology, and with DNA proximity ligation we generated a gapless assembly of one of the genomes into ten chromosomes. Whereas many filamentous pathogens display a so-called two-speed genome with more dynamic and more conserved compartments, the R. necatrix genome does not display such genome compartmentalization. It has recently been proposed that fungal plant pathogens may employ effectors with antimicrobial activity to manipulate the host microbiota to promote infection. In the predicted secretome of R. necatrix, 26 putative antimicrobial effector proteins were identified, nine of which are expressed during plant colonization. Two of the candidates were tested, both of which were found to possess selective antimicrobial activity. Intriguingly, some of the inhibited bacteria are antagonists of R. necatrix growth in vitro and can alleviate R. necatrix infection on cotton plants. Collectively, our data show that R. necatrix encodes antimicrobials that are expressed during host colonization and that may contribute to modulation of host-associated microbiota to stimulate disease development

A multi-centred randomised trial of radical surgery versus adjuvant chemoradiotherapy after local excision for early rectal cancer

Background: Rectal cancer surgery is accompanied with high morbidity and poor long term functional outcome. Screening programs have shown a shift towards more early staged cancers. Patients with early rectal cancer can potentially benefit significantly from rectal preserving therapy. For the earliest stage cancers, local excision is sufficient when the risk of lymph node disease and subsequent recurrence is below 5 %. However, the majority of early cancers are associated with an intermediate risk of lymph node involvement (5-20 %) suggesting that local excision alone is not sufficient, while completion radical surgery, which is currently standard of care, could be a substantial overtreatment for this group of patients. Methods/Study design: In this multicentre randomised trial, patients with an intermediate risk T1-2 rectal cancer, that has been locally excised using an endoluminal technique, will be randomized between adjuvant chemo-radiotherapylimited to the mesorectum and standard completion total mesorectal excision (TME). To strictly monitor the risk of locoregional recurrence in the experimental arm and enable early salvage surgery, there will be additional follow up with frequent MRI and endoscopy. The primary outcome of the study is three-year local recurrence rate. Secondary outcomes are morbidity, disease free and overall survival, stoma rate, functional outcomes, health related quality of life and costs. The design is a non inferiority study with a total sample size of 302 patients. Discussion: The results of the TESAR trial will potentially demonstrate that adjuvant chemoradiotherapy is an oncological safe treatment option in patients who are confronted with the difficult clinical dilemma of a radically removed intermediate risk early rectal cancer by polypectomy or transanal surgery that is conventionally treated with subsequent radical surgery. Preserving the rectum using adjuvant radiotherapy is expected to significantly improve morbidity, function and quality of life if compared to completion TME surgery. Trial registration:NCT02371304, registration date: February 2015

Divergent Immune Responses in Behaviorally-Inhibited vs. Non-Inhibited Male Rats

Stable behavioral traits (temperament, personality) often predict health outcomes. Temperament-specific differences in immune function could explain temperament-specific health outcomes, however, we have limited information on whether immune function varies by personality. In the present study, we examined the relationship between a basic behavioral trait (behavioral-inhibition vs. non-inhibition) and two immune responses (innate inflammation and delayed-type hypersensitivity, DTH) in a rodent model. In humans, behavioral inhibition (fearful temperament) is associated with altered stress physiology and allergies. In laboratory rats, the trait is associated with elevated glucocorticoid production. We hypothesized that behavioral inhibition is associated with glucocorticoid resistance and dampened T-helper 1 cell responses often associated with chronic stress and allergies. Further, this immune profile would predict poorly-regulated innate inflammation and dampened DTH. In male Sprague-Dawley rats, we quantified consistent behavioral phenotypes by measuring latency to contact two kinds of novelty (object vs. social), then measured lipopolysaccharide(LPS)-induced innate inflammation or keyhole limpet hemocyanin(KLH)-induced DTH. Behaviorally-inhibited rats had heightened glucocorticoid and interleukin-6 responses to a low/moderate dose of LPS and reduced DTH swelling to KLH re-exposure compared to non-inhibited rats. These results suggest that behavioral inhibition is associated with a glucocorticoid resistant state with poorly regulated innate inflammation and dampened cell-mediated immune responses. This immune profile may be associated with exaggerated T-helper 2 responses, which could set the stage for an allergic/asthmatic/atopic predisposition in inhibited individuals. Human and animal models of temperament-specific immune responses represent an area for further exploration of mechanisms involved in individual differences in health

Prognostic value of total tumor volume in patients with colorectal liver metastases:A secondary analysis of the randomized CAIRO5 trial with external cohort validation

Background:This study aimed to assess the prognostic value of total tumor volume (TTV) for early recurrence (within 6 months) and overall survival (OS) in patients with colorectal liver metastases (CRLM), treated with induction systemic therapy followed by complete local treatment.Methods: Patients with initially unresectable CRLM from the multicenter randomized phase 3 CAIRO5 trial (NCT02162563) who received induction systemic therapy followed by local treatment were included. Baseline TTV and change in TTV as response to systemic therapy were calculated using the CT scan before and the first after systemic treatment, and were assessed for their added prognostic value. The findings were validated in an external cohort of patients treated at a tertiary center. Results:In total, 215 CAIRO5 patients were included. Baseline TTV and absolute change in TTV were significantly associated with early recurrence (P = 0.005 and P = 0.040, respectively) and OS in multivariable analyses (P = 0.024 and P = 0.006, respectively), whereas RECIST1.1 was not prognostic for early recurrence (P = 0.88) and OS (P = 0.35). In the validation cohort (n = 85), baseline TTV and absolute change in TTV remained prognostic for early recurrence (P = 0.041 and P = 0.021, respectively) and OS in multivariable analyses (P &lt; 0.0001 and P = 0.012, respectively), and showed added prognostic value over conventional clinicopathological variables (increase C-statistic, 0.06; 95 % CI, 0.02 to 0.14; P = 0.008). Conclusion: Total tumor volume is strongly prognostic for early recurrence and OS in patients who underwent complete local treatment of initially unresectable CRLM, both in the CAIRO5 trial and the validation cohort. In contrast, RECIST1.1 did not show prognostic value for neither early recurrence nor OS.</p

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie