Optimal management of marine resources: spatial planning of multiple uses by multiple actors

Ocean space supplies mankind with a multitude of goods and services and yet it is under severe pressure of pollution and over-extraction of resources. To extract goods and services sustainably and to protect vulnerable ecosystems, we need to manage human activities in the marine domain. Three essential elements characterize the management of marine resources. First we are dealing with multiple uses. These uses can be conflicting, neutral or complimentary and therefore when we manage one use we should also address the effects on other uses. Second these uses are inherently spatial. Conflicts can at least partly be avoided and complementarities can be improved with careful spatial planning. Therefore we should address the spatial effects of the multiple uses when managing these activities. Third we are dealing with multiple actors. Depending on the spatial scale we look at these actors can be representatives of the several user groups that have conflicting interests, or they can be countries trying to reach agreements over the use of shared resources. In this thesis I investigate how Marine Spatial Planning and one of its tools, Marine Protected Areas (MPAs), can assist us with the management of ocean space. These instruments and their associated incentives are highly influenced by the regulatory framework, and this framework in turn depends on the spatial scale. I investigate three scale levels: the local level, defined as the Exclusive Economic Zone of a single country, the regional level, defined as a regional sea that is fully claimed by a number of countries, and the global level defined as the High Seas where all countries have access within the limits of the UN Law of the Sea. On the local level I investigate the spatial planning of offshore wind farms with an optimization model that allocates offshore wind farms under ecological constraints. The model results show that space is an essential element to derive an optimal management plan of the EEZ, because the allocation of offshore wind farms is highly dependent on both spatial economic factors such as location costs and ecological restrictions. The results show that Marine Spatial Planning is necessary, because only in this way can possible synergies between e.g. offshore wind farms and environmental protection be identified and eventually realized. The model can assist with the first steps in Marine Spatial Planning of offshore wind farms; its results can be used as a basis for conversation and consultation with stakeholders. On the regional scale I investigate how the multiple use nature of MPAs affects the incentives of countries to assign these MPAs. To this end, I develop a game theoretic model in which two specific uses, fisheries and nature conservation, by multiple countries are considered in a strategic framework. The results of the paper suggest that EU marine policy may help to secure the highest possible benefits from these MPAs, but only if policies force countries to cooperate and consider all possible benefits of MPAs. In fact cooperation on a single issue may give a worse outcome than the non-cooperative equilibrium. The results also indicate that cooperation may be hard to achieve because of defector incentives, and therefore policy measures should be strict in enforcing cooperation on all possible uses of MPAs. At the same scale level I study how species distributions and different ways of accounting for the contributions of others affects MPA assignment as a tool for biodiversity conservation. With a spatial game theoretic model I investigate three different conservation regimes: full cooperation, strategic non-cooperation, and conservation autarky. Under strategic non-cooperation countries anticipate protection by the other, under conservation autarky they ignore these contributions. The main results show that unique species occurring in a single ecosystem are relatively well protected, even when countries are free-riding. Species that occur in multiple ecosystems on both sides of the border in contrast are under non-cooperation under-protected, compared to full cooperation. This is in part caused by location leakage, i.e. protecting a number of species less because they are protected by others. On the one hand conservation autarky eliminates location leakage and generates larger MPAs at the border. On the other hand these MPA sizes are often too high from a global perspective. From this we can conclude that international conservation efforts should mainly focus on transboundary occurring species. Also, although conservation autarky is not a first-best solution, if it occurs, e.g. through social norms, it is certainly better than strategic non-cooperation. At the third level I study the effect of the assignment of internationally recognized MPAs in the High Seas on the formation of Regional Fisheries Management Organisations (RFMO) with a game theoretic model. MPAs are assigned through a weakest-link game: because everyone has to agree on an MPA before it actually can be protected, it can only be as large as the strongest opposing player wants it to be. I find that if countries have equal costs and benefits MPAs of optimal size are implemented but these have no effect on stability of RFMOs; the only stable coalition is the coalition where everyone acts alone. In the case where countries face different fishing costs, MPAs stabilize a number of extra coalitions such that more and larger coalitions are stable when an MPA is present compared to the no MPA case. Full cooperation, however, is not necessarily reached. A general conclusion is therefore that the assignment of MPAs in the High Seas can not only improve the fisheries through direct effects such as insurance and possible increases in catches, but also indirect by contributing in a positive way to the formation of RFMOs. Three important conclusions can be drawn from this thesis as a whole. First Marine Spatial Planning and Marine Protected Areas can contribute in a positive way to the management of human activities in ocean space. Second, neither of them is a silver bullet. Both need careful implementation, where all uses are accounted for, and especially the public good aspects of MPAs needs to be addressed. Third the success of MPAs (and as such of Marine Spatial Planning) is not only highly dependent on the incentives and social norms but also on the implementation scale. </p

Large Scale Marine Protected Areas for Biodiversity Conservation Along a Linear Gradient: Cooperation, Strategic Behavior or Conservation Autarky?

In this paper we investigate effects of overlap in species between ecosystems along a linear gradient on the location of marine protected areas (MPAs) under full cooperation, strategic behavior and conservation autarky. Compared to the full cooperation outcome, both strategic behavior and conservation autarky lead to under-investment in biodiversity protection. Under strategic behavior, however, we observe the additional problem of “location leakage” i.e. countries invest less in species protected by others. Conservation autarky eliminates location leakage; in ecosystems with partly overlapping species compositions at country borders it even induces MPAs that are too large from a global perspective. We also find that, in our setting of a linear gradient without migrating species, countries focus their conservation efforts on species unique to their own country and that these species are relatively well protected compared to common species

A novel UBE3A sequence variant identified in eight related individuals with neurodevelopmental delay, results in a phenotype which does not match the clinical criteria of Angelman syndrome

Background: Loss of functional UBE3A, an E3 protein ubiquitin ligase, causes Angelman syndrome (AS), a neurodevelopmental disorder characterized by severe developmental delay, speech impairment, epilepsy, movement or balance disorder, and a characteristic behavioral pattern. We identified a novel UBE3A sequence variant in a large family with eight affected individuals, who did not meet the clinical AS criteria. Methods: Detailed clinical examination and genetic analysis was performed to establish the phenotypic diversity and the genetic cause. The function of the mutant UBE3A protein was assessed with respect to its subcellular localization, stability, and E3 ubiquitin ligase activity. Results: All eight affected individuals showed the presence of a novel maternally inherited UBE3A sequence variant (NM_130838.4(UBE3A):c.1018-1020del, p.(Asn340del), which is in line with a genetic AS diagnosis. Although they presented with moderate to severe intellectual disability, the phenotype did not match the clinical criteria for AS. In line with this, functional analysis of the UBE3A p.Asn340del mutant protein revealed no major deficits in UBE3A protein localization, stability, or E3 ubiquitin ligase activity. Conclusion: The p.(Asn340del) mutant protein behaves distinctly different from previously described AS-linked missense mutations in UBE3A, and causes a phenotype that is markedly different from AS. This study further extends the range of phenotypes that are associated with UBE3A loss, duplication, or mutation

Current status and future prospects for shared decision making before and after total knee replacement surgery—a scoping review

Background. To gain insight into the current state-of-the-art of shared decision making (SDM) during decisions related to pre and postoperative care process regarding primary total knee replacement (TKR). Methods. A scoping review was performed to synthesize existing scientific research regarding (1) decisional needs and preferences of patients preparing for, undergoing and recovering from TKR surgery, (2) the relation between TKR decision-support interventions and SDM elements (i.e., team talk, option talk, and decision talk), (3) the extent to which TKR decision-support interventions address patients’ decisional needs and preferences. Results. 2526 articles were identified, of which 17 articles met the inclusion criteria. Of the 17 articles, ten had a qualitative study design and seven had a quantitative study design. All included articles focused on the decision whether to undergo TKR surgery or not. Ten articles (all qualitative) examined patients’ decisional needs and preferences. From these, we identified four domains that affected the patients’ decision to undergo TKR: (1) personal factors, (2) external factors, (3) information sources and (4) preferences towards outcome prediction. Seven studies (5) randomized controlled trials and 2 cohort studies) used quantitative analyses to probe the effect of decision aids on SDM and/or clinical outcomes. In general, existing decision aids did not appear to be tailored to patient needs and preferences, nor were the principles of SDM well-articulated in the design of decision aids. Conclusions. SDM in TKR care is understudied; existing research appears to be narrow in scope with limited relevance to established SDM principles and the decisional needs of patients undertaking TKR surgery

Adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with colon cancer at high risk of peritoneal carcinomatosis; the COLOPEC randomized multicentre trial

Background: The peritoneum is the second most common site of recurrence in colorectal cancer. Early detection of peritoneal carcinomatosis (PC) by imaging is difficult. Patients eventually presenting with clinically apparent PC have a poor prognosis. Median survival is only about five months if untreated and the benefit of palliative systemic chemotherapy is limited. Only a quarter of patients are eligible for curative treatment, consisting of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CR/HIPEC). However, the effectiveness depends highly on the extent of disease and the treatment is associated with a considerable complication rate. Methods/Design: The aim of this study is to determine the effectiveness of adjuvant HIPEC in preventing the development of PC in patients with colon cancer at high risk of peritoneal recurrence. This study will be performed in the nine Dutch HIPEC centres, starting in April 2015. Eligible for inclusion are patients who underwent curative resection for T4 or intra-abdominally perforated cM0 stage colon cancer. After resection of the primary tumour, 176 patients will be randomized to adjuvant HIPEC followed by routine adjuvant systemic chemotherapy in the experimental arm, or to systemic chemotherapy only in the control arm. Adjuvant HIPEC will be performed simultaneously or shortly after the primary resection. Oxaliplatin will be used as chemotherapeutic agent, for 30 min at 42-43 °C. Just before HIPEC, 5-fluorouracil and leucovorin will be administered intravenously. Primary endpoint is peritoneal disease-free survival at 18 months. Diagnostic laparoscopy will be performed routinely after 18 months postoperatively in both arms of the study in patients without evidence of disease based on routine follow-up using CT imaging and CEA. Discussion: Adjuvant HIPEC is assumed to reduce the expected 25 % absolute risk of PC in patients with T4 or perforated colon cancer to a risk of 10 %. This reduction is likely to translate into a prolonged overall survival. Trial registration number: NCT02231086 (Clinicaltrials.gov)

Nationwide comprehensive gastro-intestinal cancer cohorts: the 3P initiative

Background: The increasing sub-classification of cancer patients due to more detailed molecular classification of tumors, and limitations of current trial designs, require innovative research designs. We present the design, governance and current standing of three comprehensive nationwide cohorts including pancreatic, esophageal/gastric, and colorectal cancer patients (NCT02070146). Multidisciplinary collection of clinical data, tumor tissue, blood samples, and patient-reported outcome (PRO) measures with a nationwide coverage, provides the infrastructure for future and novel trial designs and facilitates research to improve outcomes of gastrointestinal cancer patients. Material and methods: All patients aged ≥18 years with pancreatic, esophageal/gastric or colorectal cancer are eligible. Patients provide informed consent for: (1) reuse of clinical data; (2) biobanking of primary tumor tissue; (3) collection of blood samples; (4) to be informed about relevant newly identified genomic aberrations; (5) collection of longitudinal PROs; and (6) to receive information on new interventional studies and possible participation in cohort multiple randomized controlled trials (cmRCT) in the future. Results: In 2015, clinical data of 21,758 newly diagnosed patients were collected in the Netherlands Cancer Registry. Additional clinical data on the surgical procedures were registered in surgical audits for 13,845 patients. Within the first two years, tumor tissue and blood samples were obtained from 1507 patients; during this period, 1180 patients were included in the PRO registry. Response rate for PROs was 90%. The consent rate to receive information on new interventional studies and possible participation in cmRCTs in the future was >85%. The number of hospitals participating in the cohorts is steadily increasing. Conclusion: A comprehensive nationwide multidisciplinary gastrointestinal cancer cohort is feasible and surpasses the limitations of classical study designs. With this initiative, novel and innovative studies can be performed in an efficient, safe, and comprehensive setting

HUMeral Shaft Fractures: MEasuring Recovery after Operative versus Non-operative Treatment (HUMMER): A multicenter comparative observational study

Background: Fractures of the humeral shaft are associated with a profound temporary (and in the elderly sometimes even permanent) impairment of independence and quality of life. These fractures can be treated operatively or non-operatively, but the optimal tailored treatment is an unresolved problem. As no high-quality comparative randomized or observational studies are available, a recent Cochrane review concluded there is no evidence of sufficient scientific quality available to inform the decision to operate or not. Since randomized controlled trials for this injury have shown feasibility issues, this study is designed to provide the best achievable evidence to answer this unresolved problem. The primary aim of this study is to evaluate functional recovery after operative versus non-operative treatment in adult patients who sustained a humeral shaft fracture. Secondary aims include the effect of treatment on pain, complications, generic health-related quality of life, time to resumption of activities of daily living and work, and cost-effectiveness. The main hypothesis is that operative treatment will result in faster recovery. Methods/design. The design of the study will be a multicenter prospective observational study of 400 patients who have sustained a humeral shaft fracture, AO type 12A or 12B. Treatment decision (i.e., operative or non-operative) will be left to the discretion of the treating surgeon. Critical elements of treatment will be registered and outcome will be monitored at regular intervals over the subsequent 12 months. The primary outcome measure is the Disabilities of the Arm, Shoulder, and Hand score. Secondary outcome measures are the Constant score, pain level at both sides, range of motion of the elbow and shoulder joint at both sides, radiographic healing, rate of complications and (secondary) interventions, health-related quality of life (Short-Form 36 and EuroQol-5D), time to resumption of ADL/work, and cost-effectiveness. Data will be analyzed using univariate and multivariable analyses (including mixed effects regression analysis). The cost-effectiveness analysis will be performed from a societal perspective. Discussion. Successful completion of this trial will provide evidence on the effectiveness of operative versus non-operative treatment of patients with a humeral shaft fracture. Trial registration. The trial is registered at the Netherlands Trial Register (NTR3617)

Adjuvant hepatic arterial infusion pump chemotherapy and resection versus resection alone in patients with low-risk resectable colorectal liver metastases - the multicenter randomized controlled PUMP trial

Background Recurrences are reported in 70% of all patients after resection of colorectal liver metastases (CRLM), in which half are confined to the liver. Adjuvant hepatic arterial infusion pump (HAIP) chemotherapy aims to reduce the risk of intrahepatic recurrence. A large retrospective propensity score analysis demonstrated that HAIP chemotherapy is particularly effective in patients with low-risk oncological features. The aim of this randomized controlled trial (RCT) --the PUMP trial-- is to investigate the efficacy of adjuvant HAIP chemotherapy in low-risk patients with resectable CRLM. Methods This is an open label multicenter RCT. A total of 230 patients with resectable CRLM without extrahepatic disease will be included. Only patients with a clinical risk score (CRS) of 0 to 2 are eligible, meaning: patients are allowed to have no more than two out of five poor prognostic factors (disease-free interval less than 12 months, node-positive colorectal cancer, more than 1 CRLM, largest CRLM more than 5 cm in diameter, serum Carcinoembryonic Antigen above 200 μg/L). Patients randomized to arm A undergo complete resection of CRLM without any adjuvant treatment, which is the standard of care in the Netherlands. Patients in arm B receive an implantable pump at the time of CRLM resection and start adjuvant HAIP chemotherapy 4–12 weeks after surgery, with 6 cycles of floxuridine scheduled. The primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival, hepatic PFS, safety, quality of life, and cost-effectiveness. Pharmacokinetics of intra-arterial administration of floxuridine will be investigated as well as predictive biomarkers for the efficacy of HAIP chemotherapy. In a side study, the accuracy of CT angiography will be compared to radionuclide scintigraphy to detect extrahepatic perfusion. We hypothesize that adjuvant HAIP chemotherapy leads to improved survival, improved quality of life, and