Financial rewards are an important driver of investment in R&D, even though many successful innovators go on to pursue objectives that extend beyond profit maximization. Universities, public-sector labs, and new classes of firms such as public benefit corporations may, in part, be motivated by a desire to contribute to social benefit. We develop a model of product innovation in a differentiated-goods duopoly, in which one firm is socially motivated, placing weight on consumer surplus as well as profit, while a rival remains profit-focused. Social motivation leads firms to price more responsibly, increasing consumer surplus and welfare for any given market structure. However, lower prices reduce profitability and can weaken incentives to undertake costly R&D. Because innovation success determines market structure, social motivation affects welfare both directly through pricing and indirectly through its effect on innovation incentives and market outcomes. We show that welfare may rise at moderate levels of social motivation but falls when reduced innovation effort leads to more concentrated markets or foregone innovation. We then characterize welfare-improving innovation policies, including R\&D tax credits and innovation prizes, and derive conditions under which one or the other instrument is fiscally preferred.

Anorectal cancer excisions can result in extensive perineal defects requiring soft tissue reconstruction. Increasing use of laparoscopic and robotic techniques to avoid laparotomy has necessitated a change in the approach to flap reconstruction. As a result, reconstructions using pedicled gracilis flaps have become a primary choice in perineal reconstruction in our unit. We have evaluated outcomes following gracilis-based reconstructions (GBR) and compared them with the more established vertical rectus abdominis myocutaneous (VRAM) to determine equivalence. We compiled retrospective data (patient demographics, perioperative management post-operative complications) on patients undergoing perineal reconstructions following colorectal surgery from 2008 to 2022. There were a total of 102 colorectal perineal reconstructions with 36 VRAM flaps and 63 GBR. There were two flap failures reported within the VRAM group, and one reported with gracilis and PAP-based reconstructions. Long term complications included two perineal hernias in the VRAM cohort, one necessitating a re-do reconstruction with bilateral pedicled gracilis flaps 112 months later. No perineal hernias were identified in the GBR cohort. Our unit has found the gracilis muscle flap to be a viable reconstruction option, favourable in its outcomes of perineal hernias. We report a few gracilis flap failures and favourable comparative outcomes to VRAM flap reconstruction. Level of evidence: Level III, therapeutic study.

The implementation of robotic assisted surgery (RAS) has brought in a change to the perception and roles of theatre staff, as well as the dynamics of the operative environment and team. This study aims to identify and describe current perceptions of theatre staff in the context of RAS. 12 semi-structured interviews were conducted in a tertiary level university hospital, where RAS is utilised in selected elective settings. Interviews were conducted by an experienced research nurse to staff of the colorectal department operating theatre (nursing, surgical and anaesthetics) with some experience in operating within open, laparoscopic and RAS surgical settings. Thematic analysis on all interviews was performed, with formation of preliminary themes. Respondents all discussed advantages of all modes of operating. All respondents appreciated the benefits of minimally invasive surgery, in the reduced physiological insult to patients. However, interviewees remarked on the current perceived limitations of RAS in terms of logistics. Some voiced apprehension and anxieties about the safety if an operation needs to be converted to open. An overarching theme with participants of all levels and backgrounds was the 'Teamwork' and the concept of the [robotic] team. The physical differences of RAS changes the traditional methods of communication, with the loss of face-to-face contact and the physical 'separation' of the surgeon from the rest of the operating team impacting theatre dynamics. It is vital to understand the staff cultures, concerns and perception to the use of this relatively new technology in colorectal surgery.

The precautionary principle justifies postponing the implementation of development projects to await better information about their environmental impacts. But if implementation capacity is congestible, as is often the case in practical settings, a postponed project may have to vie for implementation priority with projects that arrive later. Limitations of implementation capacity create two risks. First, it may sometimes not make sense to go back to a postponed project, even if it is later revealed to be a good one. Second, the planner may find it worthwhile to go back to it, but at the expense of undesirable delay of subsequent projects. We consider a planner facing a sequence of projects that vary stochastically in their (1) importance and (2) improvability, but knowing that implementation capacity is congestible. The scope for congestion implies a ‘bonus’ for earlier-than-otherwise decisions, in common parlance ‘keeping the desk clear’, which works against the well-understood option value that encourages postponement. The optimal decision rule depends upon the stochastic environment whereby future projects are generated, in ways that are not obvious. The value of the bonus is increasing in the expected importance of future projects but decreasing in their expected improvability. Higher variability of the importance of projects, in the sense of mean-preserving spread, increases the size of the bonus, but variability in their improvability has a generally ambiguous impact. We characterize the adjusted decision rule and note its implications for the conduct of cost-benefit informed policy.

BACKGROUND:A positive circumferential resection margin (CRM) after rectal cancer surgery, which can be the result of direct or indirect tumour involvement, has consistently been associated with increased local recurrence and poorer survival. However, little is known of the differential impact of the mode of tumour involvement on outcomes. METHODS:1460 consecutive patients undergoing rectal cancer resection between 2003 and 2018 were retrospectively assessed. Histopathology reports for patients with a positive CRM were reviewed to determine cases of direct (R1-tumour) or indirect tumour involvement (R1-other). Disease-free survival (DFS) and overall survival (OS) were assessed by Kaplan-Meier analysis. The role of the mode of CRM positivity was examined by univariate and multivariate Cox proportional hazards models. RESULTS:Eighty-five patients had an R1 resection due to CRM involvement (5.8%). Of those, 69 were due to direct tumour involvement, while 16 were from indirect causes. Kaplan-Meier analysis revealed that R1-other was associated with increased OS (hazard ratio 0.40, log-rank P = 0.006) and DFS (P = 0.043). Multivariate regression confirmed that the mode of CRM positivity was an independent predictor of OS. More interestingly, the patterns of recurrence were different between the two groups, with R1-tumour leading to significantly more local recurrence (P = 0.04). CONCLUSIONS:Our data strongly suggests that direct tumour involvement of the CRM confers worse prognosis after rectal cancer surgery. Importantly, differences in the site and frequency of recurrences make a case for better stratification of patients with a positive CRM to guide treatment decisions.

Editor , We present the case (Video S1) of a 72- year- old woman who 2 years previously had undergone neoadjuvant long- course radiotherapy followed by low anterior resection with covering ileostomy for treat-ment of primary rectal adenocarcinoma. During follow- up examina-tion, a lesion at the anal verge was noted. Biopsy revealed this to be a circumferential squamous cell carcinoma. MRI of the pelvis revealed a tumour at the anal verge involving the right natal cleft and introitus. CT positron emission tomography (PET) identified a single, metabolically active left inguinal node with no other evidence of distant metastatic disease (Figures 1- 3). After a multidisciplinary team meeting, the decision was made to perform completion robotic abdominoperineal resection, robotic groin node dissection and pedicled flap reconstruction of the perineum. The patient was placed in the Lloyd Davies position and the existing ileostomy was reversed. Bilateral ureteric stents were inserted. Entry to the abdominal cavity and pneumoperitoneum were achieved by an open Hasson technique at the umbilicus. On initial laparoscopy, dense adhesions between the omentum and small bowel from previous surgery were noted, limiting the insertion of standard robotic ports. Two accessory 5 mm ports were sited and laparoscopic adhesiolysis was undertaken using the Olympus Thunderbeat device. Care was taken to avoid iatrogenic injury to the small bowel. Once an adequate surgical field was achieved, robotic ports were inserted

ABSTRACTMucus secreting goblet cells play a vital role in the maintenance of tissue homeostasis. Here we report the discovery of an enigmatic mechanism for the generation of calcium signals that couple cholinergic input to secretion of hydrated mucus in the human colonic stem cell niche. Mechanistic insights for this study were derived from native human colonic crypts and crypt-like organoids expressing MUC2-mNEON. Importantly, we demonstrate that the human colonic stem cell niche is also a cholinergic niche, and that activation of muscarinic receptors initiates calcium signals at the apical pole of intestinal stem cells and neighbouring crypt-base-goblet-cells. The calcium signal ‘trigger zone’ is defined by a microdomain of juxtaposed calcium stores expressing TPC1 and InsP3R3 calcium channels. Co-activation of TPC1 and InsP3R3 is required for generation of cholinergic calcium signals and downstream secretion of hydrated mucus, which culminates in the flushing of the colonic stem cell niche.

We consider a productive network formed by agents with heterogeneous privately-known productivity types. Under convex cost of link formation, bilateral links create endogenous externalities. We calculate the "rearrangement cost" imposed on the entire network by each subset of other agents an agent can link to, and the consequent social opportunity cost of such subsets. We construct a mechanism to implement the socially optimal network, which specifies transfers based on the calculated opportunity cost, and a allocation to each agent consisting of network links. Once agents form allocated links, network connections might reveal further information to an agent on types of other agents. As a robustness check we allow pairwise adjustments under full information at the stage after forming the allocated network. We show that the mechanism is strict ex post incentive compatible, implements the optimal network as a pairwise-stable network and does not have a budget deficit.

R E FE R E N C E S 1. Ogura A, Konishi T, Cunningham C, GarciaAguilar J, Iversen H, Toda S, et al. Neoadjuvant (chemo)radiotherapy with total mesorectal excision only is not sufficient to prevent lateral local recurrence in enlarged nodes: results of the multicenter lateral node study of patients with low cT3/4 rectal cancer. J Clin Oncol. 2019;37(1):33– 43. https://doi.org/10.1200/jco.18.00032 2. Perez RO, Sao Juliao GP, Vailati BB, Fernandez LM, Mattacheo AE, Konishi T. Lateral node dissection in rectal cancer in the era of minimally invasive surgery: a stepbystep description for the surgeon unacquainted with this complex procedure with the use of the laparoscopic approach. Dis Colon Rectum. 2018;61(10):1237– 40. https://doi.org/10.1097/DCR.00000 00000 001182 3. Manabe T, Koga Y, Kubo H, Baba K, Nagayoshi K, Nagai S, et al. Adverse effects on the postoperative urinary function after combined resection of inferior vesical artery in laparoscopic lateral pelvic lymph node dissection: retrospective analysis of consecutive 95 series. Surg Laparosc Endosc Percutan Tech. 2019;29(6):493– 7. https://doi.org/10.1097/SLE.00000 00000 000681 4. Matsumoto A, Arita K. A technique of laparoscopic lateral pelvic lymph node dissection based on vesicohypogastric fascia and ureterohypogastric nerve fascia for advanced low rectal cancer. Surg Endosc. 2017;31(2):945– 8. https://doi.org/10.1007/s0046 401650147

BACKGROUND:The evidence to guide the management of asymptomatic radiologically-detected anastomotic leakages (ARAL) following anterior resection (AR) with diverting ileostomy is deficient. This study describes the outcomes of managing ARAL one of the UK teaching hospitals.METHOD:The study included all patients diagnosed with ARAL following AR during 8 years period (2012-2020). The following data were retrospectively collected: patient demographics, surgical indication, anastomotic technique, tumour staging, neoadjuvant therapy, how ARAL was managed, the outcomes and duration to heal and ileostomy reversal.RESULTS:A total of 35 patients (M = 24) who developed ARAL during the study period were included. In 32 patients, AR was performed for rectal cancer. All patients with ARAL were treated conservatively and in 31 (89%) patients, there was complete resolution of the leakage within a median duration of 6 months. Covering loop ileostomies were reversed in 26 (74%) patients with a median interval to reversal of 10 months.CONCLUSION:Most asymptomatic radiologically-detected anastomotic leakages after anterior resection heal with conservative treatment in the presence of a covering loop ileostomy with an expected average delay of 6 months for the leakage to heal before covering ileostomies can be reversed.

Competing and coexisting policies (CACPs) may arise from the incompatibility of incentives, standards, and regulatory models between a local state and a federal government, or between two government jurisdictions across which supply networks operate. Traditional studies of supply chain dynamics typically explore the impact of policy regimens as standalone instruments. This study explores how the interplay between CACP regimens can affect the supply dynamics between producers, customers, and their intermediaries. We use a supply network configuration lens to assess implications for supply chain actors and system-level outcomes. Our work is motivated by the federal-state dissonance in the current dispute between India's farmers and the federal government regarding new laws that impact agricultural supply chains in India. In this case, alternative and coexisting policy interventions, ostensibly aimed at modernizing and transforming production and distribution, can lead to significant supply chain netting and inventory pooling reconfigurations in terms of material, information, and financial flows among Indian agricultural stakeholders, along with inventory repositioning and market creation options. In addition, of significance is the consequent shift in the balance between state/nation and federal/supranational equity and bargaining power, an increasingly relevant context where supply chains operate across a common but multi-jurisdictional territory, and implications for system-level outcomes, in this particular case equity, welfare economics, and food security. We conclude by pointing to the implications of CACP regimens, and their interplay, for the broader field of operations management and supply chain research.

Total pelvic exenteration is a radical operation which involves en bloc multi visceral resection of pelvic structures including bladder, rectum, sigmoid colon and the reproductive organs. It is commonly used in gnacological cancer surgery however indications extend to recurrent rectal cancer surgery including primary advanced and recurrent cancers. The operation is challenging and radical in its nature and requires Multiple surgical specialties operating at the same time including colorectal surgeons, gynaecologist, urologist and sometimes plastic surgeons as well. Careful patient selection is of paramount importance. This video shows the importance of the procedure performed using the Da Vinci robot, a procedure that is still in its relative infancy.

The result of an extra-levator abdominoperineal excision of the rectum (ELAPE) is a composite three-dimensional defect. This is performed for locally advanced anorectal cancer, and may involve partial excision of the vagina. The aim of reconstruction is to achieve wound healing, restore the pelvic floor and to allow micturition and sexual function. We aim to evaluate the concurrent use of profunda artery perforator (PAP) and bilateral gracilis flaps for vaginal and pelvic floor reconstruction. We performed a retrospective case note review of patients undergoing pelvo-perineal reconstruction with combined gracilis and PAP flaps between July 2018 and December 2019. Eighteen pedicled flaps were performed on six patients with anal or vulval malignancies. All underwent pre-operative radiotherapy. Four patients had extended abdominoperineal tumour resections, while two patients underwent total pelvic exenteration. The median age was 57 (range 47-74) years, inpatient stay was 22 (11-47) days and the follow-up was 10 (5-21) months. Four patients developed partial perineal wound dehiscence, of which one was re-sutured. One patient had a post-operative bleed requiring radiological embolisation of an internal iliac branch and had subsequent 1cm PAP flap loss. All other flaps survived completely. Median time to heal was 4 (1-6) months. This is the first series reporting combined bilateral gracilis and PAP flaps for pelvic reconstruction. The wound dehiscence rate and healing times were expected in the context of irradiation and radical pelvic tumour resection. This is a reliable technique for perineal and vaginal reconstruction with minimal donor site morbidity. (C) 2021 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Total pelvic exenteration is a radical operation which involves en bloc multi visceral resection of pelvic structures including bladder, rectum, sigmoid colon and the reproductive organs. It is commonly used in gnacological cancer surgery however indications extend to recurrent rectal cancer surgery including primary advanced and recurrent cancers. The operation is challenging and radical in its nature and requires Multiple surgical specialties operating at the same time including colorectal surgeons, gynaecologist, urologist and sometimes plastic surgeons as well. Careful patient selection is of paramount importance. This video shows the importance of the procedure performed using the Da Vinci robot, a procedure that is still in its relative infancy.

Closure of an abdominal stoma, a common elective operation, is associated with frequent complications; one of the commonest and impactful is incisional hernia formation. We aimed to investigate whether biological mesh (collagen tissue matrix) can safely reduce the incidence of incisional hernias at the stoma closure site.In this randomised controlled trial (ROCSS) done in 37 hospitals across three European countries (35 UK, one Denmark, one Netherlands), patients aged 18 years or older undergoing elective ileostomy or colostomy closure were randomly assigned using a computer-based algorithm in a 1:1 ratio to either biological mesh reinforcement or closure with sutures alone (control). Training in the novel technique was standardised across hospitals. Patients and outcome assessors were masked to treatment allocation. The primary outcome measure was occurrence of clinically detectable hernia 2 years after randomisation (intention to treat). A sample size of 790 patients was required to identify a 40% reduction (25% to 15%), with 90% power (15% drop-out rate). This study is registered with ClinicalTrials.gov, NCT02238964.Between Nov 28, 2012, and Nov 11, 2015, of 1286 screened patients, 790 were randomly assigned. 394 (50%) patients were randomly assigned to mesh closure and 396 (50%) to standard closure. In the mesh group, 373 (95%) of 394 patients successfully received mesh and in the control group, three patients received mesh. The clinically detectable hernia rate, the primary outcome, at 2 years was 12% (39 of 323) in the mesh group and 20% (64 of 327) in the control group (adjusted relative risk [RR] 0·62, 95% CI 0·43-0·90; p=0·012). In 455 patients for whom 1 year postoperative CT scans were available, there was a lower radiologically defined hernia rate in mesh versus control groups (20 [9%] of 229 vs 47 [21%] of 226, adjusted RR 0·42, 95% CI 0·26-0·69; p<0·001). There was also a reduction in symptomatic hernia (16%, 52 of 329 vs 19%, 64 of 331; adjusted relative risk 0·83, 0·60-1·16; p=0·29) and surgical reintervention (12%, 42 of 344 vs 16%, 54 of 346: adjusted relative risk 0·78, 0·54-1·13; p=0·19) at 2 years, but this result did not reach statistical significance. No significant differences were seen in wound infection rate, seroma rate, quality of life, pain scores, or serious adverse events.Reinforcement of the abdominal wall with a biological mesh at the time of stoma closure reduced clinically detectable incisional hernia within 24 months of surgery and with an acceptable safety profile. The results of this study support the use of biological mesh in stoma closure site reinforcement to reduce the early formation of incisional hernias.National Institute for Health Research Research for Patient Benefit and Allergan.

Purpose Malignant large bowel obstruction is a surgical emergency that requires urgent decompression. Stents are increasingly being used, though reported outcomes are variable. We describe our multidisciplinary experience in using stents to manage malignant large bowel obstruction. Methods All patients undergoing colorectal stent insertion for acute large bowel obstruction in a teaching hospital were included. Outcomes, complications, and length of stay (LOS) were recorded. Results Over a 7-year period, 73 procedures were performed on 67 patients (37 male, mean age of 76 years). Interventional radiology was involved in all cases. Endoscopic guidance was required in 24 cases (32.9%). In 18 patients (26.9%), treatment intent was to bridge to elective surgery; 16 had successful stent placement; all had subsequent curative resection (laparoscopic resection, 8 of 18; primary anastomosis, 14 of 18). Overall LOS, including both index admission and elective admission, was 16.4 days. Treatment intent was palliative in 49 patients (73.1%). In this group, stents were successfully placed in 41 of 49 (83.7%). Complication rate within 30 days was 20%, including perforation (2 patients), per rectal bleeding (2), stent migration (1), and stent passage (5). Nineteen patients (38.8%) required subsequent stoma formation (6, during same admission; 13, during subsequent admission). Overall LOS was 16.9 days. Conclusion In our experience colorectal stents can be used effectively to manage malignant large bowel obstruction, with only selective endoscopic input. As a bridge to surgery, most patients can avoid emergency surgery and have a primary anastomosis. In the palliative setting, the complication rate is acceptable and two-thirds avoid a permanent stoma.

Programs that certify the environmental (or other social) attributes of firms are common. But the proliferation of labeling schemes makes it difficult for consumers to know what each one means-what level of "greenness" does a particular label imply? We provide the first model in which consumers can expend effort to learn what labels mean. The relationship between information acquisition costs, firm pricing decisions, the market shares obtained by alternatively labeled goods and a brown "backstop" good, and total environmental impact proves complex. Consumer informedness can have perverse implications. In plausible cases a reduction in the cost of information damages environmental outcomes. Our results challenge the presumption that provision of environmental information to the public is necessarily good for welfare or the environment.

We consider a model in which productive bilateral links are formed between heterogeneous agents who differ in their innate productivity. Local information is complete but an outside planner can observe only network properties. We ask if consistent credit rating -- where agents' ratings are increasing in their productivity -- is possible using network characteristics alone. The key to our results is that the network structure is endogenous since the use of agents' network neighborhood properties in generating ratings also impacts their incentives for link formation. Network structure and credit scores are therefore determined jointly in equilibrium. We show that if the cost of link formation is not too low, there is a pairwise stable equilibrium under credit rating where the network structure is a connected nested split graph (CNSG) with neighborhood size increasing in type. This is also the unique equilibrium if we consider a class of "truthtelling" equilibria (that is, equilibria in which the network structure separates types, enabling consistent credit rating). Further, among networks that separate types, this specific CNSG constitutes precisely the optimal structure.