Over the last 20 years, surgical training in the United Kingdom (UK) has changed dramatically. There have been considerable efforts towards creating a programme that delivers the highest standard of training while maintaining patient safety. However, the journey to improve the quality of training has faced several hurdles and challenges. Recruitment processes, junior doctor contracts, flexible working hours and equality and diversity have all been under the spotlight in recent times. These issues, alongside the extended surgical team and the increasingly recognised importance of trainee wellbeing, mean that postgraduate surgical training is extremely topical. Alongside this, as technology has evolved, this has been incorporated into all aspects of training, from recruitment to simulated training opportunities and postgraduate examinations. The coronavirus (COVID-19) pandemic has brought technology and simulation to the forefront in an attempt to compensate for reduced operative exposure and experience, and has transformed the way that we learn and work. In this article, we reflect on the UK surgical trainee experience and discuss areas of success as well as highlighting potential areas for improvement going forward. Surgical training initially began as an apprentice-style model with no specific duration of or defined career progression . The CalAs it stands, UK medical graduates enter into foundation year (FY) training for 2 years, upon completion of which they have full registration with the General Medical Council (GMC) and are eligible to apply for core surgical training (CST) at national selection to a programme either ‘coupled’ with a higher surgical training post  or a standalone ‘uncoupled’ 2-year post. Some surgical specialties  can progress directly into specialty training see Fig. . Prior tFor trainees interested in a career in academic surgery, after graduating from medical school, trainees can apply for a 2-year Specialised Foundation Programme, previously known as Academic Foundation Programme. The programme focuses on research, leadership and management or medical education . TraineeIn the UK, surgical education is managed regionally by Local Education and Training Boards. The Joint Committee on Surgical Training (JCST) is responsible for curriculum development and quality assurance of all the surgical training programmes in the ten defined surgical specialities via Specialty Advisory Committees: Cardiothoracic Surgery, General Surgery, Neurosurgery, Oral and Maxillofacial Surgery, Otolaryngology, Paediatric Surgery, Plastic Surgery, Trauma and Orthopaedics, Urology and Vascular Surgery. The end of training is marked by the award of a ‘Certificate of Completion of Training’ (CCT) which requires completion of the intercollegiate fellowship examinations, completion of surgical training competency-based assessments, demonstration of management and leadership skills and logbook evidence as outlined by the JCST. The trainees pay a tax-deductible annual fee of £260 to JCST to maintain an electronic portfolio that is monitored by clinical and educational supervisors.There are currently 4 Royal Colleges in the UK: The Royal College of Surgeons of England (RCS Eng), The Royal College of Surgeons of Edinburg (RCS Ed) and The Royal College of Physicians and Surgeons of Glasgow (RCPSG). The Royal Colleges offer a range of educational and training resources for both the UK and international trainees. Some colleges were established in the early 1500 s and have continued to provide learning and advancement in surgery. The membership or fellowship exams are a key step in training progression, awarding full membership status provides a title of ‘Miss/Ms/Mr’ for successful trainees. Royal Colleges play a crucial role in developing the surgical curriculum, lobbying for trainees and promoting and supporting surgical training.Since the publication of the Lancet Commission on Global Surgery , all colThe Association of Surgeons in Training (ASiT) is an independent professional body that works to promote the highest standards in surgical training . It was The Global Anaesthesia, Surgery and Obstetric Collaboration (GASOC) organisation was formed in 2015 following the launch of the Lancet Commission on Global Surgery. This interdisciplinary trainee advocacy group raises awareness about the lack of access to surgical and perioperative care in low and middle-income countries (LMIC) [After medical school graduation, trainees are faced with high debts over a 20-year period . The cosThe reduction in elective operating as a result of the COVID-19 pandemic has meant that trainees have been forced to look for other opportunities to maintain and develop technical skills . In addiAt a postgraduate level, surgical teaching can occur through formal departmental programmes or ad hoc case-based learning, in both a clinical and outpatient setting. With the start of the COVID-19 lockdown, face-to-face events were stopped and this provided a significant challenge for trainees to continue their educational activities. Instead, the focus moved to the virtual ‘classroom’, face-to-face presentations moved to online webinars, allowing trainees to attend live and recorded teaching sessions from internationally renowned speakers covering a vast range of topics, from live operating sessions to journal club discussions and examination revision courses. The advantage of an online platform provides flexibility to the modern surgical trainee, enabling them to listen at their convenience and continue the learning process.Surgical conferences are another key area of postgraduate training that have been transformed into a virtual format as a result of the COVID-19 era. Similar to webinars, online conferences allowed trainees to attend national and international events to present their work at a time when travel was not permitted. New virtual platforms also enabled interaction and networking that face-to-face conferences encourage, providing junior doctors and aspiring trainees the opportunity to ask key questions of their peers and seniors.Trainees have several options to take time out of training to learn and develop or take a career break . Out of Surgical training is for everyone. Women in surgery experience various forms of discrimination and a perceived ‘glass ceiling’ during their surgical training . EffortsSurgical trainees are prone to burnout, stress and psychiatric illness. This has been exacerbated due to COVID-19 effects, leading to poor performance and also impacting on patient care . The RoyAlthough there have been many challenges facing surgical trainees, the greatest being the ongoing COVID-19 pandemic, this period has also brought forward new opportunities, accelerated the transition of surgical training into the virtual world and encouraged advancement of novel training solutions, including simulation strategies.


ABSTRACT IMPACT: Recognizing Interdisciplinary Collaborative Research in Promotion and Tenure Processes OBJECTIVES/GOALS: Academic institutions have traditionally focused on individual achievements for promotion. We present our effort on identifying and measuring attitudes on promotion and tenure (PT) criteria that values and rewards interdisciplinary research (IR). We have developed a toolkit to facilitate the recognition of IR in PT processes. METHODS/STUDY POPULATION: Our group reviewed appointment, promotion and tenure (APT) policies from each of the six Health Science Schools and the College of Engineering at the University of Washington (UW) to assess language of objective criteria and attributes of IR to guide APT committees in the evaluation of interdisciplinary researchers. We surveyed faculty about their attitudes relating to IR within the context of promotion and tenure. Interviews of department chairs and administrators about institutional policies and infrastructure that supports or inhibits IR, and current best practices, were conducted. We have developed toolkits for junior faculty, department chairs, external reviewers, and APT committees to facilitate rewarding IR at promotion. RESULTS/ANTICIPATED RESULTS: Review of APT policies found criteria that recognizes IR for APT in three schools. 118 faculty responded to the survey . The majority of faculty reported they were currently conducting IR (95%), considered IR important (98%), and believed the UW faculty code should encourage IR (85%). Although a vast majority considered their units supportive of IR (>80%), less than half (43%) reported that their APT criteria provided examples that included participation in IR. Our survey also found that APT committees were challenged about best practices to reward IR, APT external reviewers struggle to evaluate individual vs team contributions, and individual faculty are challenged to describe contributions for APT within context of an interdisciplinary team. DISCUSSION/SIGNIFICANCE OF FINDINGS: IR is conducted and valued by UW faculty; however, current structures, policies, and APT code do not facilitate IR for promotion and tenure. We have developed a toolkit for promotion-eligible faculty, chairs, external reviewers, and APT committees to facilitate IR. Our goal is to modify UW faculty code and unit APT criteria to recognize and reward IR.


European forest policymaking is shaped by progressing European integration, yet with notable ideological divisions and diverging interests among countries. This paper focuses on the coalitional politics of key environmental forest issues: biodiversity conservation, timber legality, and climate protection policy. Combining the Advocacy Coalition Framework and the Shifting Coalition Theory, and informed by more than 186 key informant interviews and 73 policy documents spanning a 20-year timeframe, we examine the evolution of coalitional forest politics in Europe. We find that the basic line-up has remained stable: an environmental coalition supporting EU environmental forest policy integration and a forest sector coalition mostly opposing it. Still, strategic alliances across these coalitions have occurred for specific policy issues which have resulted in a gradual establishment of an EU environmental forest policy. We conclude with discussion of our findings and provide suggestions for further research.The online version contains supplementary material available at 10.1007/s13280-021-01644-5. Forest issues in the European Union (EU) and its Member States (MS) have been subject to policy controversy for decades. In particular, biodiversity conservation and forest management are disputed along an ideological forestry-environmental division spanning across the EU multi-level governance system. The dispute concerns trade-offs regarding multiple forest ecosystem services, such as biomass for the bioeconomy and rural development .Change in EU environmental forest policy is rare unless a coalition skilfully exploits changes in the framework conditions for a policy reform (“Policy stability” Hypothesis).Our third hypothesis draws on the SCT propositions:Depending on the policy issue at stake, dynamic processes of (re-) building strategic alliances occur across different advocacy coalitions .An advocacy coalition is composed of state and non-state actors that coordinate actions to implement their shared beliefs into policy. These beliefs include, for instance, basic value priorities regarding groups or other entities whose welfare is of greatest concern, beliefs about the nature and severity of the policy problem and about who is responsible for appropriate problem solutions  decision-making authority, (b.) money, (c.) information, (d.) supportive public opinion, (e.) mobilization of supporters, and (f.) skilful leadership  frequently supports domestic implementation of EU policy through EU compliance and enforcement actions under the legal threat of infringement procedures. The Commission also assesses experiences with the domestic implementation of existing EU policies, evaluates their effectiveness and proposes further EU policy changes : Changes in EU environmental forest policy entail a mixture of core beliefs from various coalitions that are dependent on each other to influence policy in the complex EU policy making system .S1–S6. For all the three case studies, 186 semi-structured interviews were conducted with key informants representing EU institutions, MS authorities, environmental NGOs, forest and landowner enterprises, timber traders, forest sector industry and scientists. Policy documents included official documents , coalition members’ published material , and previous research  (Cresswell 2005).Our policy research draws on qualitative content analysis of interviews and documents. References to those numbered interviews  and documents  can be found in the text, especially at the end of each paragraphs and in the process-tracing tables. Further details are placed in the Electronic Supplementary Material (ESM), Tables 1) or cooperative politics through shifting coalitions (X2), the use of different power resources  or institutional venues , as well as their effects on policy development such as policy change (Z1) or policy stability (Z2)  with their effects on policy development that manifest in different policy outcomes (Z) Beach . DrawingTo identify coalitions, we identified policy actors’ beliefs as expressed in written statements and interviews. In addition, actors were asked to identify other actors that they cooperate with, and actors they saw as their opponents in the policy process. Cooperation among actors was also cross-checked through documents such as co-signed letters, reports, and statements (Cresswell 2005).In late 1980s, an environmental coalition of non-state and state actors from national and EU levels  officially adopted the new EU biodiversity law in May 1992 Sharp . The EU The opposition coalition was poorly organized. Forest sector interest groups from forest-rich countries (France and Germany) did not engage as they were not yet organized at the EU level  to perform sufficiency checks and request improvements in selected sites. Notably, only evidence from conservation science was to be considered to protect or restore, at favorable conservation status, natural and semi-natural habitats. The Habitats Directive also obliges MS to introduce a strict system of protection for certain plant and animal species, which also applies beyond designated protected areas , the European Environment Agency (EEA), the European Topic Center on Biodiversity (ETSB), MS environmental public authorities as well as environmental NGOs and scientists worked together to support policy implementation. They assessed MS proposals for Natura 2000 protected areas and demanded expansions. The members of the forestry and land use coalition were not part of official decision-making venues due to the primacy of ecological criteria in establishing the Natura 2000 network (I27-37).Enforcement challenges became evident soon after the MS had to implement the Directive against increasing land users’ opposition across almost all MS. Related to forestry, this opposition resulted in neglect or inappropriate legal transpositions of the formal rules, delayed and insufficient designations of protected areas, and questionable conservation management. The Commission/DG ENV took legal actions against non-compliant MS. With almost 20 years delay, the formal area designations are now largely completed. The Natura 2000 network today constitutes more than 26,000 sites, half of which are located in and/or depend on forest ecosystems. This means that one fourth of all EU’s forests are now protected in the Natura 2000 network .The widespread resistance from land use actors led the environmental coalition to temporarily mute its top-down conservation biology implementation beliefs, and to engage in strategic cooperation with the forestry and land use coalition in the 2000s. National environmental authorities sought to work together with landowners, hunters, and concerned citizens within EU and MS expert working groups. This resulted, for instance, in voluntary Natura 2000 contracts with compensation payments in some MS. The top-down regulatory approach was, however, never fully abandoned, and repeated legal procedures enforced the protection of Natura 2000 sites in forests .Coalitional politics during the fitness check were marked by significant cross-coalitional shifts Table . The forDuring that period, the environmental coalition formed a strategic alliance with a third policy coalition consisting of non-bioeconomy businesses such as wind power energy, electricity, cement and construction industries. This cross-coalitional “contra change” alliance argued for the intrinsic value of nature, like the environmental coalition. It further underlined that changes in the Nature Directives might lead to legal uncertainties for businesses, preventing sustainable development. Still, it requested flexible implementation from MS, like the forestry and land use coalition. This constellation eventually resulted in a defeat of the “pro-change” bioeconomy coalition of forestry and land use actors at the end of the Fitness Check .The polarization between the environmental and the forestry and land use coalitions currently continues after the Commission launched a new EU Biodiversity Strategy to 2030 and a new EU Forest Strategy, setting more ambitious conservation targets and claiming a clearer EU forest decision-making power under the environmental competence, goals that meet with opposition by state forestry authorities in some forest-rich MS. Linking biodiversity conservation and climate change mitigation, the new EU Biodiversity Strategy aims to extend the existing Natura 2000 network of protected area, including stricter protection of primary and old-growth forests. While both strategies aim for more ambitious biodiversity conservation targets than in the past, their impact on forestry and conservation practices in the MS remains to be seen given recent heated debates surrounding them and their implementation .Table Public awareness of tropical deforestation grew in the 1980s and 1990s, and illegal logging gained increased political attention after the G8 countries tackled the issue with their Action Programme on Forests in 1998 under the UK Presidency (D1). Similar to the Natura 2000 case, a coalition of environmental NGOs  formed and strategically framed illegal logging as an issue experienced abroad mostly in tropical countries, but connected to drivers operating “at home” in the EU marketing and consuming illegally sourced wood products .As a response, the Commission and MS jointly adopted the EU’s FLEGT Action Plan in 2003, favoring voluntary “supply-side” economic incentives to tropical countries. This mainly included FLEGT voluntary partnership trade agreements (VPAs) with the EU , requesting successful multi-stakeholder negotiations about good governance and national timber legality definitions, as well as establishing timber tracking systems in tropical countries in exchange for preferred EU market access for tropical wood and wood products from the respective partner country (I82-83).Subsequently, environmental NGOs, but also some countries and specifically UK pushed for additional policy measures. For instance, in 2004, 180 NGOs, scientists and citizens from Europe, Russia and Asia, led by Greenpeace, signed a joint statement requesting new EU legislation to “outlaw imports of all illegally sourced timber products into the EU market”. Environmental groups also stated that the “issue of forest sustainability needs to be addressed” since “legal and illegal logging are often closely linked and (…)legal logging can be highly destructive”, and because the forest industry would be “unable to regulate itself and is destroying forests and peoples' livelihoods on a grand scale” (D26). Later, NGOs worked together with European timber companies and retailers  to sign a series of FLEGT industry statements calling EU institutions and Member States to adopt a new EU law to make it “illegal to import all illegally sourced timber and wood products into the European market”, while stimulating fair competition and sustainable markets (D4).In response, the Commission (DG ENV) carried out assessments and consultations on future EU policy options against illegal logging, which showed that the bilateral VPA negotiations were slower than expected, and that further EU legislative actions were needed to strengthen the policy against illegal logging (D1). In September 2008, the governments of UK, the Netherlands and Denmark, supported by Austria, Bulgaria, Germany, Romania, and Luxembourg, requested the Commission to publish a communication on additional legal options, including a proposal for EU legislation .In October 2008, the Commission presented a first EU legislative proposal emphasizing industry self-regulation through a due diligence approach of risk management along timber supply chains . The Commission stressed its intention to simplify the requirements for economic operators and national authorities while stimulating economic competitiveness (D1). In response, NGOs and the environmentally oriented branches of the Commission  built a cross-coalitional alliance with timber importing industries, big multinational timber retail companies and national authorities from forest-poor timber importing MS  to demand a stricter EU Timber Regulation (EUTR) that would ban illegally sourced timber from entering the EU market (prohibition). Interestingly, this cross-coalitional alliance did not advocate for additional mandatory sustainability rules, as initially requested by NGOs. This mirrored a strategic concession from the environmental groups toward their industry partners. The industry groups, on their part, saw the strategic collaboration with NGOs as a chance to revert the image of tropical timber, portrayed by NGOs and scientists to be of risky or criminal origin .A forest sector coalition composed of domestic forestry interest groups, national forestry state authorities from forest-rich export-oriented countries  and economically oriented branches of the Commission (DG TRADE and DG AGRI) mobilized to oppose to the EUTR in general, and to a prohibition clause in particular. They rejected any EU legal measures on the demand side that could affect businesses, and opposed creating a precedent of EU environmental competency in forestry matters that would constrain rights to commercially use forests and timber resources. They argued that the European forest sector was fully committed to sustainable forest management, and requested the use of supply-side measures (FLEGT VPAs), voluntary industry self-regulation (codes of conduct) and market incentives (forest certification) to tackle the “outside” illegal logging problem .A subsequent Commission’s proposal for a stronger EUTR with a prohibition clause became subject to heated political debates in Council meetings and the Parliament from 2008 onwards. Despite the resistance of the forest sector coalition members, the Council, the European Parliament and the Commission finally adopted the EUTR in July 2010 after three informal trialogue meetings and two years of tough political negotiations. The Parliament had threatened to not finalize the legislative process without inclusion of a prohibition clause, and to extend the scope of the regulation toward mandatory forest sustainability standards. Subsequently, the EUTR-supportive Spanish and Belgian governments, holding the Council Presidencies in 2010, brokered a political compromise between the Parliament, the Council and the Commission in that the prohibition would be the price of a deal to not include sustainability standards, and also emphasizing that the prohibition would have high symbolic importance .The European Parliament passed the EUTR with 644 votes in favor, 25 votes against and 16 abstentions. In the final vote in the Council under the Presidency of Belgium in October 2010, all MS voted for, with only Sweden voting against, with the Czech Republic and Portugal abstaining .A summary of the policy advocacy coalitions and shifting coalitions in the EU FLEGT/EUTR policy for the period 2004–2020 is provided in Table Similar to EU Natura 2000 policy, the domestic implementation of the EUTR has been slow, and an overall lack of enforcement is evident in several MS. During its domestic implementation, coalitions and strategic alliances have partly continued to shift, and partly ceased, while the ideological confrontation between environmental and industry actors relating to sustainability vs. legality remains , the Parliament (COMENVI) and forest-poor MS  expressed the need to complement the EUTR with a new EU legal instrument to control forest-risk agricultural supply chains to help achieving biodiversity conservation and climate protection goals. Forest industry actors in the forest-poor countries  remained concerned about market disadvantages due to the incoherent implementation of the EUTR (D32-34).Recently, the Commission/DG ENV and the Parliament/ENVI Committee started formulating a new EU legal framework for action against  deforestation and forest degradation. Building on the EUTR, this currently evolving legal framework suggests mandatory due diligence rules for forest-risk agricultural  and timber commodities that are placed on the EU market. Beyond legality verification, this may also include sustainability standards relating to environmental and human rights protection. This new legal framework would respond to the fact that nearly 80% of tropical deforestation is related to agricultural expansion in response to global food demand, including EU consumption. Nevertheless, the ideological framing division of timber legality versus forest sustainability remains also in this recent debate (D34).Table Until ca. 2010, EU institutions and member states hesitated to include forestry and agriculture in climate policy, as this was regarded to be too complex, uncertain, and difficult to regulate  as a benchmark to assess future carbon sink efforts from forestry and land use in the 2021–2030 period based on a projected continuation of traditional forest management practices from 2000 to 2009 (instead of 1990 to 2009), and not penalizing emissions from forest aging and climate-induced forest damages . The Regulation also acknowledges the climate benefits of (intensive) forest use and wood products, which can store carbon and substitute for emission-intensive materials .2 from the atmosphere, known as the “no debt rule”. In line with this, the regulation establishes a legally binding EU policy for how MS should measure emissions and removals from management practices in their forests. This decision addresses earlier criticism from environmental groups that emissions from biomass in energy production were not accounted for under previous EU policy, e.g., the Renewable Energy Directive—RED I and RED II (D19).At its core, the LULUCF regulation obliges MS to ensure that accounted GHG emissions from the LULUCF sector are balanced by at least an equivalent accounted removal of COThe final policy outcome reflected a mixture of the beliefs of three policy advocacy coalitions. A first coalition formed to secure what they believed to be the environmental integrity of the LULUCF Regulation. This coalition included environmental and climate NGOs , conservation biology and climate protection scientists, as well as the Commission (DG ENV) and the Parliament (COMENVI), accompanied by some MS environmental and nature protection public authorities. Initially several coalition members opposed the inclusion of the LULUCF sector in EU climate policy as they feared that this may dilute climate policy efforts. They were open to inclusion of the LULUCF in the EU reduction commitments only on the condition that there would be separate mandatory carbon reduction targets, full accounting for leakage or “hidden emissions”, including from bioenergy, accounting of harvested wood products that would address uncertainties, and forest management accounting based on the historical period of 1990–2012. They also advocated for legally binding EU rules safeguarding that carbon is enhanced in standing (mature and old growth) forests while promoting environmental integrity in forest management, protected forest areas, and ecological restoration .The environmental integrity coalition was pitted against a more influential forest bioeconomy coalition. The latter was not only composed of forestry sector actors and forestry scientists at the EU and national levels . A range of national public forestry authorities representing forest-rich countries with economically important national forest sectors  as well as like-minded branches of EU institutions such as the Commission (DG AGRI) and the Parliament (COMAGRI) were also active members in this forest bioeconomy coalition. This coalition supported timber-use-oriented forestry and material/energy substitution with wood-based products, strategically framed as positive climate mitigation action. They also pressed for national level decision-making flexibility in implementing the EU’s LULUCF accounting rules. They called for national forest sector strategies, as well as for forest reference levels (FRLs) based on historical forest use, and communicated studies that not harvesting timber would enhance risks that carbon stored over decades in forests is released due to climate change driven forest disasters .The Commission (DG CLIMA) and national public authorities in countries where forestry and environmental interests were similarly powerful  or where climate-environmental interests overrode forestry interests  formed a third, pro-climate EU regulation policy coalition. This coalition skilfully merged the (polarized) positions of the other two coalitions. On the one hand, they accepted that the environmental integrity coalition was not taking the diversity of national forest situations into account, and hence supported some national flexibility in line with the claims of the forest bioeconomy coalition. On the other hand, they criticized the forest bioeconomy coalition for being too slack regarding environmental integrity, and hence supported a mandatory EU LULUCF accounting approach with some environmental safeguards and decision-making by the Commission .The climate policy coalition could eventually find a compromise between the other coalitions during the negotiations and final adoption of the LULUCF Regulation between 2016–2018. They built a strategic cross-coalitional alliance with national agricultural authorities and interest groups in forest-extensive but agriculture-intensive EU countries . These agricultural actors considered the Commission’s legal proposal as an opportunity to compensate for emissions from the agriculture sector through carbon offsets either in their own forests  or in other MS’ forests .The three policy advocacy coalitions were not entirely stable during the negotiation and adoption process of the LULUCF regulation. For instance, a shift in the French, German and Swedish positions from a contra-regulatory/pro-forest bioeconomy to a pro-climate regulatory position followed from political changes in governments with new commitments to act against climate change, along with the policy spill-over impacts from the LULUCF commitments in the Paris Agreement in 2015. France and Germany played a major role in finding a compromise, while Finland and many Eastern European countries remained quite stable in their pro-forest bioeconomy and national flexibility beliefs (I7-14).A summary of the policy advocacy coalitions and shifting alliances  is provided in Table Between late 2019 and 2020, the Commission developed an overarching EU climate neutrality and climate smart economy policy with the adoption of the European Green Deal and the 2030 Climate Target Plan. This EU climate policy aims to cut GHG emissions by at least 55% by 2030, and adopts a legally binding commitment to make the EU-27 climate neutral by 2050. Therein, the Commission and MS recognize the importance of forests in achieving climate goals and request stepping up policy, legal and practical climate action in the LULUCF sector (D20-22).In October 2020, the Commission amended the existing LULUCF legislation with a delegated act setting FRLs that each country must apply between 2021 and 2025. It remains to be seen, however, how national implementation of the LULUCF regulation will progress given complex technical rules and recently enhanced timber removals partially related to forest disturbances reducing forest sinks in several EU countries Table .Table 7PHow can we explain both change and continuity in EU environmental forest policy over time from a coalitional politics perspective?stable line-up of competing advocacy coalitions—and namely a forestry and an environment coalition—that differ fundamentally regarding their core beliefs. These coalitions have strongly influenced the policy debates and outcomes of EU environmental forest policy in all three issue areas. The ideological divergence between environmental and forest use policy advocacy coalitions is evident not only among MS authorities, but also within the EU institutions.The empirical evidence from all three cases supports the “Adversarial coalitional politics” Hypothesis 1 in that EU environmental forest policy is characterized by a Specifically, our findings show that the environmental coalition consists of environmental NGOs who tend to liaise both with each other and like-minded EU institutions  and with national environmental authorities that are strong domestically specifically in forest-poor countries with weak forest industries and strong NGOs . They share normative beliefs concerning biodiversity conservation and support tackling global sustainability challenges. They advocate environmentally oriented regulatory EU polices to advance their beliefs, and oppose MS flexibility and non-legally binding policies giving leeway to commercial use of forests. Southern EU MS  tend to share similar environmental core beliefs, but support stronger EU forest environmental policy also for the expectation of EU financial support to tackle issues of rural land abandonment, non-profitable forestry and climate change problems such as droughts and fires  tend to liaise with like-minded EU institutions . This forest use coalition tends to oppose common EU forest policy, especially if it would be based under an environmental competency. Instead, it supports active forestry, and prefers flexible forest-economy friendly policies under MS competency.These findings mirror similar insights for a large set of policy studies  or engages in a cross-ideological strategic alliance building (Hypothesis 3). Concretely, the first case could be observed for the agenda setting and policy adoption phase of the Habitats Directive in the early 1990s: Here, the success of the nature protection coalition was connected to their ability to strategically use opportunities of the EU system (Council and Commission venues in the EU-12), spillovers from international biodiversity policy, new conservation science evidence as well as changes in governments to translate its conservation beliefs into the EU Nature Directives. Later on, when the two new EU environmental forest policies (FLEGT and LULUCF) emerged, such strong influence of the environmental coalition was no longer observed.Hence, except for the adoption phase of the Habitats Directive, our findings support Hypothesis 3 according to which strategic alliances occur across different advocacy coalitions and are a precondition for policy change. These cross-coalitional alliances—also labeled Baptist and Bootlegger (B&B) coalitions in the political economy literature Yandle —were buiFinally, all three case studies (except to some degree the Natura 2000 adoption phase) confirm our fourth hypothesis in that changes in EU environmental forest policy will entail a mixture of core beliefs from various coalitions as outcome of strategic alliance building and compromises that were necessary to achieve policy change. In sum, with the help of such alliances and despite the opposition of the forestry and land use coalition, the environmental coalition was able to establish EU environmental forest policies in all three investigated issue areas.What remains to be further explored, beyond the scope of this paper, is how such a gradual success of the environmental coalition at the EU policy level is counterbalanced by reluctant implementation at the level of MS. Existing research shows that dissatisfied MS and interest groups from the forestry and land use coalitions have been partly able to revert successes of the environmental coalition through weakening practical implementation and mitigating policy impact on the ground  a stable long-term line-up of rivaling policy advocacy coalitions that are characterized by fundamentally different policy core beliefs and related  interests—with an environmental vis a vis a forest use coalition being most central; (ii.) dynamic processes of forming strategic alliances across different policy advocacy coalitions in relation to specific policy issues that evolve over time; and (iii.) changes in EU’s environmental forest policy that reflect the multi-faceted translation of policy core beliefs of involved actors’ coalitions.In a forward-looking perspective, there is little doubt that cross-coalitional conflicts will endure in EU environmental forest policy and possibly intensify Below is the link to the electronic supplementary material.


Domnik et al.; Phillips et al.; James et al.). Thus, the overarching objective of the current Research Topic series was to review some of these recent advancements in CPET methods and interpretation and to discuss their relevance, in both clinical and research settings, in patients with various respiratory conditions.The value of cardiopulmonary exercise testing (CPET) is well-established as an adjunct to clinical evaluation. Worldwide, exercise “stress” testing is vastly under-utilized, especially for individuals with pulmonary disorders. This is lamentable because modern refinements in the measurements of physiological impairment during CPET have improved our ability to evaluate such patients more comprehensively (VO2)—a key metric of exercise performance—and an independent predictor of mortality in various cardio-pulmonary disorders , well before physiological maxima are actually attained . Thus, measurement of exertional symptoms, using validated scales, is integral to any assessment of exercise capacity .Uniquely, CPET can identify specific abnormalities of the integrated metabolic, cardiopulmonary, locomotor muscle, and neurosensory systems, under graded physiologic stress. Based on foundational physiological principles, CPET interpretation has traditionally focused on measuring peak oxygen uptake  .Recent experimental work during CPET examined the simultaneous associations between inspiratory neural drive (IND) to the respiratory muscles, dynamic respiratory mechanics and subjective breathing discomfort and has shed light on fundamental mechanisms of exercise limitation in health and various respiratory conditions (2 (VE/VCO2) is linked to increased IND and dyspnea intensity and is common to several respiratory conditions, including chronic obstructive pulmonary disease (COPD) , interstitial lung disease (ILD),  and pulmonary arterial hypertension (PAH) . It is no surprise, therefore, that VE/VCO2 is increasingly represented in CPET interpretative algorithms . High VE/VCO2 nadir  generally indicates presence of poor ventilatory efficiency, due to high physiological dead space (and compromised lung CO2 elimination), alveolar hyperventilation (enhanced chemo-sensitivity) or both. Measurement of arterial partial pressure of CO2 (PaCO2), and not end-tidal CO2, , is needed to determine the relative contribution of each to high VE/VCO2. As repeatedly highlighted in this series, VE/VCO2 must be considered in the context of the prevailing mechanical constraints, which can blunt the normal ventilatory response and compound interpretation. For simplicity, measurement of VE/VCO2nadir is the preferred parameter: it generally occurs at relatively low exercise intensities, when arterial O2 saturation is normal and before the onset of both metabolic acidosis (with ventilatory compensation) and significant restrictive mechanical constraints on tidal volume (VT) expansion . The combination of operating lung volumes [measured by serial inspiratory capacity (IC) maneuvers] and breathing pattern can help detect important inspiratory mechanical constraints, which are relevant to dyspnea and exercise limitation , especially in milder forms of obstructive and restrictive disorders or other cardio-respiratory conditions . The lower the resting IC, the closer VT is positioned to total lung capacity (TLC) and to the upper extremity of the respiratory system's sigmoidal pressure-volume relation. Thus, as VT expands to occupy ~70% of IC and inspiratory reserve volume (IRV) reaches its minimal value, higher IND and breathing effort is needed to achieve a given VT. This reflects the increased elastance of the respiratory system, when breathing close to TLC. Appearance of the VT inflection or plateau , as a function of increasing VE during exercise, is an important mechanical event and heralds the onset of NMD and an abrupt rise in dyspnea. As resting IC diminishes over time in obstructive and restrictive disorders, critical inspiratory mechanical constraints and onset of dyspnea will occur at progressively lower VE during exercise  and taught us that exercise response pattern abnormalities are surprisingly similar, despite vastly different pathological origins. For patients referred with unexplained exertional dyspnea, who do not manifest any of the described abnormal patterns during CPET, alternative diagnoses such as dysfunctional breathing of psychogenic origin should be considered . We hope that the pragmatic approach to CPET proposed here will help the clinician to individualize management plans by providing clear answers to a few key questions: how severe is dyspnea and exercise intolerance in my patient?; is ventilatory demand increased and if so, why?; and are dynamic mechanical abnormalities present that contribute to poor exercise performance?This series has provided a comprehensive physiological characterization of patients with COPD, ILD, and PAH, (DEO wrote the first draft of the manuscript. All authors were responsible for critically reviewing the manuscript for intellectual content and approved the final version of the manuscript submitted for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The 2020 COVID-19 pandemic has disrupted Alzheimer’s disease (AD) clinical studies worldwide. Digital technologies may help minimize disruptions by enabling remote assessment of subtle cognitive and functional changes over the course of the disease. The EU/US Clinical Trials in Alzheimer’s Disease (CTAD) Task Force met virtually in November 2020 to explore the opportunities and challenges associated with the use of digital technologies in AD clinical research. While recognizing the potential of digital tools to accelerate clinical trials, improve the engagement of diverse populations, capture clinically meaningful data, and lower costs, questions remain regarding the stability, validity, generalizability, and reproducibility of digital data. Substantial concerns also exist regarding regulatory acceptance and privacy. Nonetheless, the Task Force supported further exploration of digital technologies through collaboration and data sharing, noting the need for standardization of digital readouts. They also concluded that while it may be premature to employ remote assessments for trials of novel experimental medications, remote studies of non-invasive, multi-domain approaches may be feasible at this time. The 2020 COVID-19 pandemic disrupted clinical trials worldwide as health care facilities became overwhelmed and lock-down conditions shuttered clinical trial sites, forcing both study staff and trial participants to stay home . Nearly Study sponsors have responded to these challenges in different ways; for example, by mailing drugs to trial participants to ensure participants have access to interventions; limiting clinic visits through the establishment of alternative trial sites; allowing a brief hiatus from dosing; and implementing home infusions. Funders have also responded with innovations. In an analysis of their funding portfolio during the latter half of 2020, the Alzheimer’s Drug Discovery Foundation (ADDF) found that about 70% of grantees expected their studies to be delayed, and some requested no-cost extensions. Delays may harm not only budgets but data analyses as well, since data interpretation can be muddled due to long-term disruptions, missing data, and protocol deviations; with clinical studies more affected than preclinical studies. Observational studies have also been affected. For example, Swedish BioFINDER2 halted enrollment, and the Rush University aging cohort studies stopped performing autopsies due to lack of PPE. In response to these challenges, the Alzheimer’s Association introduced a Rapid Program in Dementia (RAPID) funding program to provide bridge funding for Association-funded research during the pandemic.In March 2020, the U.S. Food and Drug Administration (FDA) issued guidelines on the conduct of clinical trials during the pandemic and updated this guidance in December 2020 . The guiIn recent years, digital technologies that enable remote assessment and gather real-world granular data on a variety of cognitive and functional outcomes have received increased attention and interest in the AD drug development community . RecogniEven if there were no pandemic, clinical trials as currently conducted are too slow and costly to adequately respond to a disease such as Alzheimer’s, which currently affects around 50 million people worldwide and for which there is no approved disease-modifying treatment . The difHowever, converting trial outcomes from in-person to remote measures is also associated with many challenges. Among the most critical aspects to be considered are usability and the reliability and fidelity of technology-related measures . ConsumeIn the AD space, digital tools have shown particular promise in capturing subtle cognitive and functional changes in preclinical AD. Yet there remain questions regarding their ability to serve as outcome measures due to questions around feasibility, reliability, and validity.As the COVID-19 pandemic has necessitated moving clinical trials from specialized centers to home-based virtual assessments using both passive and active measures, investigators are learning lessons that have the potential to accelerate all clinical trials for dementia. Indirect measures of behavior, function, and physiology are being explored as cognitive and functional endpoints for clinical trials by individual research groups as well as technology companies. For example, Elektra Labs has created the Atlas platform, which takes a data science approach to clinical trials through the application of a wide selection of connected sensors and physiological and behavioral markers.Many research groups that have developed and/or implemented digital technologies in clinical studies presented data and plans to the Task Force, providing lessons learned as well as strategies for moving forward:The Collaborative Aging Research Using Technology (CART) Initiative funded by the US National Institutes of Health and the Department of Veterans Affairs, has developed a multi-functional digital assessment platform that is technology agnostic, use case flexible, sharable, and scalable . The plaIn two separate cohorts, digital data streams provided by the CART ORCATECH platform demonstrated changes in mood (through online self-reported questionnaires) and physical activity (through actigraphy) that coincided with the imposition of stay-at-home orders because of the pandemic.The public private partnership Remote Assessment of Disease and Relapse — AD (RADAR-AD), funded by the Innovative Medicines Initiative (IMI) has embraced an “internet of things” (IOT) approach similar to the CART/ORCATECH system to measure early decline in cognitive function using low friction digital devices across a range of challenges. A study is planned that will enroll 200 participants over age 50 including those with preclinical AD, MCI due to AD, mild-to-moderate AD, and age and gender matched controls. RADAR earlier launched a multi-site prospective cohort study to determine the feasibility, usability, and acceptability of remote measurement technology (RMT) for major depressive disorder (MDD) .Remote digital measurements that may be used in RADAR-AD include adaptations of multiple instruments to be administered using a table or smartphone interface such as the Amsterdam-instrumental activities of daily living questionnaire (A-IADL-Q)  to assesThe RADAR base app, using a smartphone and passive sensors, will assess mobility, social communication, time at home, general activity, and sleep duration and quality. A residential movement detector will also assess gait and mobility at home and time spent in different areas of the home. The Mezurio smartphone app will capture high-frequency data related to cognition, including sleep, planning, memory, mood and anxiety, voice and speech, and typing and swiping .In its search for sensitive measures of subtle cognitive decline in preclinical AD, The Harvard Aging Brain Study (HABS) developed an iPad-based Computerized Cognitive Composite (C3) and subsequently a smartphone-based tool for remote assessment of memory. The C3 on the iPAD comprises 3 components: a Behavioral Pattern Separation task, a Face-Name Associative Memory Exam, and the Cogstate Brief Battery. Development of the C3 included its use in the A4 study, a secondary prevention trial in clinically normal older adults with abnormal levels of amyloid who were randomized to receive placebo or solanezumab. This initial study showed that when the drug was administered in screening period, the amyloid-positive group performed worse on C3 compared to the Preclinical Alzheimer Cognitive Composite (PACC) , 17. TheHABS has also developed the Boston Remote Assessment for Neurocognitive Health (BRANCH), which combines two paired associative learning tasks, an associated memory test, and a continuous visual recognition task accessible on a smartphone. In a recent study, BRANCH was shown to be correlated with scores on the paper-based preclinical Alzheimer’s cognitive composite (PACC5) .HABS investigators have also been using BRANCH to assess learning curves using data from clinically normal older adults who completed 5 consecutive days of BRANCH. Early evidence suggests that a steeper learning curve is associated with better performance on the PACC, although the results were not statistically significant. Nonetheless, capturing learning curves using a smartphone over several days appears to be feasible and valid and may be useful to prescreen potential trial participants for biomarker status and identify those at greater risk for imminent cognitive decline and most likely to benefit from treatment. Cognitive learning curves may also serve as a paradigm for exploring psychopharmacokinetic profiles of medications to assess for efficacy over relatively short time periods.The Trial-Ready Cohort for Preclinical and Prodromal Alzheimer’s Disease (TRC-PAD) was established to accelerate drug development for AD by ensuring timely recruitment of targeted individuals into optimally designed preclinical and prodromal trials. TRC-PAD gathers multiple types of data including digital data from wearables and sensors through its informatics platform (TRC-PAD IP). In concert with TRC-PAD, the Alzheimer’s APT Webstudy registry was established along with an analytics platform, a referral management system, and a data management system .The APT Webstudy has been working to optimize digital smartphone-based tools to assess cognition, such as the Cogstate Brief Battery. The study plans to implement this tool in the AHEAD 3–45 secondary prevention trials in early preclinical and preclinical AD and in the CT1812 trial in early AD . APT is In its World Report on Healthy Ageing, the World Health Organization (WHO) redefined healthy aging in terms of functional ability, which is a product of an individual’s intrinsic capacity (IC) interacting with the environment . In ordeWith a goal of improving clinical trial recruitment, the Brain Health Registry (BHR) was established in 2014 as a website and online registry that collects digital data from potential clinical trial participants and study partners through self-report questionnaires and neuropsychological tests. Among the over 70,000 individuals enrolled in BHR, there have been over 106,000 referrals and 5,000 enrolled in other clinical studies. Through co-enrollment, BHR and clinical trial data can be linked.BHR is also involved in methods development and validation of new online methods, including an electronic Clinical Dementia Rating (CDR) scale, a digital financial capacity instrument, and other digital assessment tools. In support of blood biomarkers studies, BHR has also collaborated with Quest Diagnostics to scale up blood collection using remote identification through the registry.Many other clinical research programs are exploring using digital measures of cognition and function . For example, the Framingham Heart Study (FHS) is developing a smartphone platform with multiple applications including digital voice. Voice (spoken utterances and language) is measured through device agnostic technologies and FHS research shows that linguistic and acoustic measures can be used as biomarkers of cognitive function –28. HoweThe Deep and Frequent Phenotyping (DFP) study in the United Kingdom has also incorporated digital measures from wearables and smartphones to capture highly granular data on gait, memory, navigational ability, and other measures that may serve as proxies for cognition and function . The stuDigital devices offer the potential to expedite clinical trials, reduce the sample sizes or duration of studies, lower the cost of acquiring and analyzing data, enable the recruitment of more diverse and representative populations, reduce the need for specialized raters, reduce rater burden, and increase the clinical meaningfulness of outcome data collected to determine efficacy of an intervention. During a pandemic, digital tools also may provide the means for remote assessments, which could mitigate problems associated with closure of clinical trial sites and the safety concerns associated with in-person assessments and interventions.Combining cognitive and functional endpoints in clinical trials is well established through the use of questionnaires in symptomatic stages of disease; and in preclinical disease, reports from both participants and study partners regarding high-level functional activities appear to provide valuable information on disease trajectory. Pairing digital cognitive measures with digital functional assessments may offer increased sensitivity in preclinical disease. The HABS team has shown that functional inventories can be administered remotely through the use of REDCap software, saving time and reducing data errors without sacrificing data quality.They allow data to be time stamped, which enables assessment of everyday function.They can improve participant compliance by providing study participants and partners with reminders to take medications and engage in study-related activities.Audio and video recordings can provide a level of biometric validation to ensure that study participants themselves (rather than study partners) are providing data.Passive sensing of activities such as driving and computer use have demonstrated unique personalized patterns that can be captured using relatively simple algorithms.Passive sensors reduce participant burden, thus potentially reducing drop-outs and producing outcomes that are easily understandable and relevant in a real-world context.Meta-data such as time taken to complete a questionnaire or remember to take medication on time may also reflect changes in episodic memory, a key domain affected in AD.Passive assessment of sleep may prove useful since disrupted sleep has been shown to be a mediator of amyloid deposition in many studies.The technologies employed in various digital devices provide additional potential advantages:To achieve the promise of digital devices will require addressing many challenges including those related to reliability, validation, user acceptability, regulatory approval, privacy and security. While regulators have indicated a willingness to consider digital data, much work remains to be completed before digital measures are accepted as primary or secondary outcomes. Indeed, the FDA issued guidance on the conduct of trials during a pandemic which includes increased flexibility around trial procedures intended to maintain participant safety, but less flexibility around efficacy measures. Task Force members also questioned whether regulators would accept remotely acquired data where there is no assurance that study participants and not study partners completed questionnaires or cognitive outcome assessments.While digital registries may enable outreach to otherwise under-represented populations, engagement and retention of trial participants through digital means alone may be insufficient. Indeed, studies have reported high compliance rates that they attribute to personalized rather than anonymous digital engagement of study participants .Transitioning cognitive assessments to smartphones may enable more frequent and sensitive measurement among large numbers of participants in a short period of time. However, smartphones may introduce additional challenges with regard to data fidelity and security. Other technological challenges related to digital data include the difficulty of analyzing continuous data and deconvoluting diverse data captured by devices. Addressing these challenges will be advanced by wider collaboration with the computer science and data science community.Digital readouts are diverse and non-standardized, which results in impediments to data aggregation and sharing of data, both of which are essential to advance the field. Collaboration among technology developers is needed to ensure that raw data from which readouts on different devices are derived will be made available to the research community. Privacy concerns represent an additional roadblock to data sharing. Federated data management platforms have been developed that provide researchers with access to multiple types of data from multiple sources . The AlzDespite the challenges of conducting clinical studies during the pandemic, the AD clinical research community remains committed to advancing current studies and launching new studies. Indeed, Task Force participants suggested that the COVID-19 experience may fuel preparations for better clinical trials that mitigate both the risks associated with the pandemic and more common complications of clinical trials for example by broadening the reach of recruitment efforts.Among the possibilities discussed by the Task Force was the potential to design completely digital or hybrid trials combining virtual/telemedicine and physical visits. For example, telemedicine consultations in the pre-screening phase of a trial could help verify inclusion and exclusion criteria, provide information to potential trial participants, and obtain electronic consent. Virtual visits could also be used for trial components that do not require technically invasive procedures. The INSPIRE study team at Toulouse University Hospital tested this strategy following the first COVID lockdown in France and found a high rate of acceptance among participants .Digital devices may provide new analytical methods as well, for example, by enabling assessment of intraindividual change in a high frequency way. Digital tools implemented during the pandemic may also provide increased understanding to the effects of daily stress, anxiety, and poor sleep on cognitive outcomes. They may also enable continued assessment of cognitive function in participants post-infection with COVID-19.To ensure that clinical studies continue through the pandemic and its aftermath, the Task Force recommended that regulators and institutional review boards provide guidance yet maintain flexibility with regard to changes in applications/devices and statistical plans and allow for virtual and home-based visits and remote monitoring. Developers must consider alternate or additional trial sites, and funders should expect unanticipated modifications to protocols and funding needs.The Task Force concluded its session with a discussion of the field’s readiness to conduct remote clinical trials. Task Force members urged caution in employing remote assessments for trials of experimental medications; the digital measures at this time may be most productively embedded in parallel with conventional measures in early-stage Phase 1 and 2 trials, demonstrating their fidelity or even superiority to current commonly used clinical outcome measures. Enthusiasm was expressed for using digital technologies in remote studies of non-invasive interventions such as studies of vitamins, exercise, and mind-body or multidomain approaches. Trials of repurposed drugs for which safety data exists may also be feasible as entirely remote trials. For example, because of the COVID-19 pandemic, the Alzheimer’s Disease Cooperative Study (ADCS) is attempting to conduct the PEACE-AD (prazosin for disruptive agitation in Alzheimer’s disease) trial  as a rem


As part of the process of updating national dietary reference values (DRVs) and food-based dietary guidelines (FBDGs), the Nordic Nutrition Recommendations 2022 project (NNR2022) will select a limited number of topics for systematic reviews (SRs).To develop and transparently describe the results of a procedure for prioritisation of topics that may be submitted for SRs in the NNR2022 project.In an open call, scientists, health professionals, national food and health authorities, food manufacturers, other stakeholders and the general population in the Nordic and Baltic countries were invited to suggest SR topics. The NNR2022 Committee developed scoping reviews (ScRs) for 51 nutrients and food groups aimed at identifying potential SR topics. These ScRs included the relevant nominations from the open call. SR topics were categorised, ranked and prioritised by the NNR2022 Committee in a modified Delphi process. Existing qualified SRs were identified to omit duplication.n = 21), ‘Medium’ (n = 9) or ‘Low’ (n = 22) importance, and the PI/ECOTSS statements with ‘High’ were ranked in a Delphi process. The nine top prioritised PI/ECOTSS included the following exposure–outcome pairs: 1) plant protein intake in children and body growth, 2) pulses/legumes intake, and cardiovascular disease and type 2 diabetes, 3) plant protein intake in adults, and atherosclerotic/cardiovascular disease and type 2 diabetes, 4) fat quality and mental health, 5) vitamin B12 and vitamin B12 status, 6) intake of white meat (no consumption vs. high consumption and white meat replaced with red meat), and all-cause mortality, type 2 diabetes and risk factors, 7) intake of n-3 LPUFAs from supplements during pregnancy, and asthma and allergies in the offspring, 8) nuts intake and cardiovascular disease (CVD) and type 2 diabetes in adults, 9) dietary fibre intake (high vs. low) in children and bowel function.A total of 45 nominations with suggestion for more than 200 exposure–outcome pairs were received in the public call. A number of additional topics were identified in ScRs. In order to omit duplication with recently qualified SRs, we defined criteria and identified 76 qualified SRs. The NNR2022 Committee subsequently shortlisted 52 PI/ECOTSS statements, none of which overlapped with the qualified SRs. The PI/ECOTSS statements were then graded ‘High’ (de novo SRs is central in the NNR2022 project, as the results of these SRs may cause adjustment of existing DRVs and FBDGs. That is why we have developed this extensive process for the prioritisation of SR topics. For transparency, the results of the process are reported in this publication.The selection of topics for The principles and methodologies developed in the NNR2022 project may serve as a framework for national health authorities or organisations when developing national DRVs and FBDGs. This collaboration between the food and health authorities in Denmark, Estonia, Finland, Iceland, Latvia, Lithuania, Norway and Sweden represents an international effort for harmonisation and sharing of resources and competence when developing national DRVs and FBDGs. Qualified systematic reviews will be the main foundation for revising dietary reference values and food-based dietary guidelines in the Nordic Nutrition Recommendation 2022.de novo systematic reviews by the Nordic Nutrition Recommendation 2022 project.This paper describes the results of an open, transparent six-step procedure to identify topics that will be prioritised for Systematic reviews (SRs)  are the In the field of cancer, the World Cancer Research Fund International (WCRF) regularly produces qualified SRs on diet, obesity and physical activity and their causal relationship with the 17 most common cancers . The ‘Dide novo SRs, which adhere to the extensive principles and methodologies for qualified SRs.In the NNR2022 project, we have considered multiple health outcomes from 51 nutrient or food group exposures, representing in total several hundred possible exposure–health outcome pairs. Thus, the available qualified SRs from national food and health authorities and international food and health organisations cover only a subset of all possible nutrient/food group relationships with the main outcomes considered when setting DRVs and FBDGs in the NNR2022 project. The NNR2022 project plans to use the available budget to develop a limited set (i.e. 9) of ad hoc procedure when prioritising topics for SRs. Recently, a more systematic and transparent approach has been set out . Forty-Whilst only a limited number of topics made it through to the final list of SR prioritisations due to limited resources, all public nominations will be evaluated carefully by the NNR2022 Committee and various chapter experts when the DRVs and FBDGs are developed and formulated.de novo SRs, members of the NNR2022 Committee performed 51 scoping reviews (ScRs), one for each of the nutrients and food group chapters that will be part of the final NNR2022 report. An ScR is a relatively new approach to explore existing evidence  when appropriate.An evaluation of the results of the open public call (Electronic Supplementary Table 1) was included in each relevant ScR. Each ScR was considered by the NNR2022 Committee. The final version of the ScRs was formulated in a consensus process after several rounds of consultations in the NNR2022 Committee.The criteria for shortlisting and prioritisation included evidence of significant new and relevant research since the previous edition of NNR (NNR2012)  and releBox 1Criteria for shortlisting and prioritisation of topics for de novo SRs.Relevance: The topic is within the scope of NNR2022.Within scope (examples): Healthy populations/individuals; prevention purposes ; covers different age groups, and pregnant and lactating women; increased requirements during short-term mild infections; etc.Outside scope (examples): Long-term infections; malabsorption; various metabolic disturbances; treatment of persons with a sub-optimal nutritional status; clinical guidelines on dietary supplementation.Importance: The topic has new, relevant and significant data or is an emerging topic in an area of substantial public health interest or concern.Substantial public health concern (examples): Overweight, obesity and adiposity-related illness; metabolic syndrome and diabetes mellitus type 2; atherosclerotic cardiovascular diseases; cancer; osteoporosis; neurodegenerative diseases; mental health; oral health; multi-morbidity and mortality; reproductive health; optimal growth.Relevant and significant: Refers to the overall scientific quality of the evidence, the number of studies, consistency of results and whether new study results appear to expand the DRV- and FBDGs-related information available in the previous edition of NNR.Potential national impact: The SR may potentially inform national food and health policies and programs. An SR with the specific topic may result in a new or an adjustment of previous DRVs or FBDGs.If the research question is within the scope of NNR2022 and covers an outcome of substantial health concern to the Nordic and Baltic countries, then it has potential national impact. In other words, it may inform DRVs, FBDGs and national food and health policies and programs.No duplication: The topic is not currently addressed through other recent qualified SRsIn order to omit duplication of recent qualified SRs, we established a process to identify relevant qualified SRs. The definition of a qualified SR was based on the inclusion and exclusion criteria  pre-specBox 2Inclusion and exclusion criteria for qSRs in the NNR2022 project.Inclusion criteria for SRs:Commissioned by national food or health authorities, or international food and health organisationAuthored by a group of multidisciplinary expertsConsist of an original systematic review of the evidence for a nutrient/diet-health relationshipIncludes at least one nutrient/food topic and its relationship to at least one outcome related to a chronic disease or condition that is of public health interest in Nordic of Baltic countries; includes a clear description of the systematic review methodology, which should be similar to the methodology used NNR2022 Includes an assessment of the quality of primary studiesProvides an evidence grade for the overall quality of the evidenceEnglish languageRecent: Refer to SRs that have been published after the previous edition of the NNRExclusion criteria for SRs:Commissioned or sponsored by industry or an organisation with a business or ideological interestAuthors with strong ties to industry or ideological organisationsLater updated in another qualified SR on the same topicFocused on an outcome outside the scope of the NNR (e.g. disease management or food safety)The search for qualified SRs was based on searches in PubMed/Medline and inspection of the websites of national and international food and health authorities as described by the Food and Agriculture Organization (FAO) of the United Nations . We alsoNational Academy of Sciences, Engineering and Medicine, USADietary Guidelines Advisory Committee, USAWorld Health Organization (WHO)World Cancer Research Fund (WCRF)European Food Safety Agency (EFSA)Scientific Advisory Committee on Nutrition (SACN), UKGerman Nutrition Society, GermanyHealth Council, The NetherlandsNational Health and Medical Research Council, AustraliaMinistry of Health, New ZealandHealth Canada, CanadaAll identified qualified SRs that fulfilled the inclusion and exclusion criteria are listed in All shortlisted topics from the ScRs and the public call were formulated by the NNR2022 Committee as initial PI/ECOTSS statements . The shon = 21), ‘Medium’ (n = 9) or ‘Low’ (n = 22) importance . The NNR2022 Committee and the topic experts (i.e. the scientists recruited to author the respective nutrient or food group chapters in NNR2022) will be consulted when finalising the protocols.A protocol –21 will de novo SRs is central in the NNR2022 project, as the results of these SRs may cause adjustment of existing DRVs and FBDGs. That is why we have developed this extensive process for prioritisation of SR topics. The current paper describes the results of this procedure used to prioritise topics for de novo SRs in the NNR2022 project. The nine prioritised PI/ECOTSS statements include the following exposure–outcome pairs: 1) plant protein intake in children and growth, 2) pulses/legumes, and cardiovascular disease and type 2 diabetes, 3) plant proteins, and atherosclerotic/cardiovascular disease and type 2 diabetes, 4) fat quality and mental health and 5) vitamin B12 and vitamin B12 status, 6) intake of white meat (no consumption vs. high consumption and white meat replaced with red meat), and all-cause mortality, type 2 diabetes and risk factors, 7) intake of n-3 LPUFAs from supplements during pregnancy and asthma and allergies in the offspring, 8) nuts intake, and CVD and type 2 diabetes in adults, 9) dietary fibre intake (high vs. low) in children and bowel function  used to develop the 51 ScRs. We decided initially to limit the search to reviews published in 2011 and later with the filter ‘Humans’. If the search resulted in ≥500 items, we limited the search to papers with the nutrients or food groups in the title. If still ≥500 items, we included the additional requirements: ‘Diet’ OR ‘Dietary’ OR ‘FOOD’ OR ‘Nutrition’ OR ‘Nutritional’. If still ≥500 items, we limited the search to only include ‘Systematic reviews’. The reason why we initially selected to search for reviews published after 2010 is that it is likely that a topic with significant new and relevant data would have been discussed in a review paper published after the search date in the previous edition of NNR. In this type of strategy, we omit all original publications. However, DRVs or FBDGs are seldom, or never, revised based on one or a few original publications. In the present literature search process to identify SR topics, only original study results found important enough to be cited and discussed in review papers are candidate for SR topics.Additionally, if a large number of reviews were identified for a single nutrient or food group (i.e. ≥500 papers), we added sequentially additional relevant limitations, simply to reduce the burden of the authors of the 51 ScRs. In total, 13,992 reviews were identified and scrutinised by the ScR authors. Although we do not believe that other topics would have been prioritised with an even more comprehensive search strategy, we cannot rule out the possibility that some important topics have been missed.de novo SRs. In each of the 51 nutrient and food group chapters that will be part of the final NNR2022 report, a separate literature search will be performed and described.It is important to note that the present literature search was only used to select topics for The organisation, the principles and the methodologies developed in the NNR2022 project build on processes similar to other national authorities or international health organisations. The procedure described in this paper, together with the three previous principle and methodology papers from the NNR2022 project , may serA large amount of resources and extensive interdisciplinary front-edge competence is needed to develop national DRVs and FBDGs. No or few single nations have these qualifications alone. Thus, international collaboration and global harmonisation of methodological approaches are highly needed. The NNR2022 project, which is a collaboration between the food and health authorities in Denmark, Estonia, Finland, Iceland, Latvia, Lithuania, Norway and Sweden, represents such an international effort for harmonisation and sharing of resources and competence.de novo SRs in the NNR2022 project. The nine prioritised PI/ECOTSS include the following exposure–outcome pairs: 1) plant protein intake in children and body growth, 2) pulses/legumes intake, and cardiovascular disease and type 2 diabetes, 3) plant protein intake in adults, and atherosclerotic/cardiovascular disease and type 2 diabetes, 4) fat quality and mental health, 5) vitamin B12 and vitamin B12 status, 6) intake of white meat (no consumption vs. high consumption and white meat replaced with red meat), and all-cause mortality, type 2 diabetes and risk factors, 7) intake of n-3 LPUFAs from supplements during pregnancy and asthma and allergies in the offspring, 8) nuts intake, and CVD and type 2 diabetes in adults, 9) dietary fibre intake (high vs. low) in children and bowel function.SRs are the preferred method to summarise the causal relationship between nutrient or food group exposure and a health outcome. They are the main fundament for developing DRVs and FBDGs. In this paper, we describe the results of an open, transparent six-step procedure to identify and prioritise topics most appropriate for Click here for additional data file.


Mucopolysaccharidoses are a group of lysosomal storage disorders that are caused by deficiency of enzymes involved in glycosaminoglycans degradation. Due to low prevalence and high childhood mortality, researches on mucopolysaccharidoses were mainly focused on the fatal manifestations. With the development of treatments, more and more mucopolysaccharidoses patients were treated by approved therapies, thereby getting prolonged life span and improved quality of life. Abnormal accumulation of glycosaminoglycans in the eye may block trabecular meshwork, thicken sclera and change mechanical behavior of lamina cribrosa, which, by increasing intraocular pressure and damaging optic nerve, could cause glaucoma. Glaucoma was the leading cause of irreversible blindness worldwide, but it was rarely reported in mucopolysaccharidoses patients. Although non-fatal, it seriously affected quality of life. Prevalence of glaucoma in mucopolysaccharidoses patients (ranged from 2.1 to 12.5%) indicated that glaucoma in patients with mucopolysaccharidoses was worthy of attention and further study, thereby improving the quality of life for MPSs patients. Mucopolysaccharidoses (MPSs) are rare lysosomal storage disorders that are caused by abnormal accumulation of glycosaminoglycans (GAGs), which is due to deficiency of enzymes involved in degradation of GAGs . MPSs arDue to low prevalence and high childhood mortality of MPSs, researches were mainly focused on the fatal manifestations. Governments typically stimulated development of specific therapies for MPSs by providing regulatory and economic incentives. For example, enzyme replacement therapies for non-neuronopathic forms of MPS I and II have been developed and approved to date . Life spGlaucoma, as a leading cause of irreversible blindness, is a group of eye conditions that are characterized by progressive degeneration of retinal ganglion cells , 9. GlauGlaucoma was known to be related with MPS I –17, MPS Clinical manifestations of MPSs were caused by abnormal accumulation of GAGs, which were long and unbranched heteropolymers with repeating disaccharide units that were made up of carbohydrate moiety of proteoglycans . GAGs weThe main risk factor for glaucoma is increased IOP, which may be caused by dysfunction of trabecular meshwork (TM) Fig. A. TM locNumerous GAGs and proteoglycans were expressed in TM . At leasThe relationship between GAGs and TM was not only studied at the animal level, but also explored at the cell level. Proliferation and fibronectin expression of TM cells were affected by pore size, alignment and composition of GAGs. This work provided insight into how the architecture and composition of collagen-GAGs scaffolds affected TM cells behavior .Open angle glaucoma may be caused by abnormal GAGs deposition within TM, while angle closure glaucoma may result from abnormal accumulation of GAGs in anterior segment structures and/or ciliary body cysts , 37 FigB. GlaucoCoudrillier et al. 2012) reported that thickness and biomechanical response differed between human glaucoma eyes and normal eyes . Contrib2 reporteEvaluation of optic nerve head (ONH), where retinal ganglion cell axons exit in the eye, is important for diagnosis and management of glaucoma . Stress Patients with MPSs could develop glaucoma due to abnormal accumulation of GAGs, yet it was rarely reported in those patients. The following reasons could account for this phenomenon: (1) life span of patients with MPSs was usually not long enough to show obvious clinical manifestations of glaucoma; (2) non-ocular clinical manifestations of MPSs, including cognitive impairment and bone diseases, hindered diagnosis of glaucoma; (3) corneal clouding could block examination of inner contents of eyes and affect IOP measurement.Age is an established risk factor for glaucoma . Except Non-ocular clinical manifestations of MPSs were also obstacles to diagnosis of glaucoma. Clinical manifestations of MPSs that blocked communication, including hearing loss and mental-retardation, may hinder doctors from understanding the condition of patients with MPSs , 48. MPSCorneal clouding, which was caused by abnormal accumulation of GAGs in corneal, did not block communication but could hinder diagnosis of glaucoma . It was IOP should be tested by the same, individually adjusted and well-tolerated devices during follow-up of MPSs patients since different tonometry methods may result in variable IOP-values. Goldmann applanation tonometry, the gold standard for IOP measurement, was less dependent on corneal properties, making it more reliable for measuring IOP of patients with MPSs . Ocular A group of paediatric ophthalmologists, an orthoptist and an optometrist with extensive experience in children with MPSs, held a meeting in Stockholm in September 2010 and drew up clinical guidelines for diagnosis and management of ocular manifestations of MPSs . The guiTreatments for glaucoma in MPSs patients could follow the clinical guidelines for glaucoma: (1) initial therapy was topical medication or laser trabeculoplasty; (2) if patients failed to attain the target IOP during follow-up, additional therapies should be considered, such as trabeculectomy, non-penetrating deep sclerectomy and/or other glaucoma surgeries . In addiCurrent knowledge about the benefits and risks of anti-glaucoma therapies for MPSs patients is limited, because MPSs patients with glaucoma were rarely reported. A multicenter retrospective case note review reported the impact of medical treatments on IOP of 12 eyes from MPSs patients with glaucoma: IOP of 7 eyes was reduced; 1 eye was less successfully treated; 2 eyes stopped receiving treatment; IOP of 1 eye was reduced after keratoplasty . The res(1) Reports of glaucoma in MPSs patients were rare; reports about results of anti-glaucoma therapies for MPSs patients with glaucoma were rarer. Limited data hampered efforts to have a full view of prevalence of glaucoma in MPSs patients, benefits and risks of anti-glaucoma therapies, among other aspects. (2) Pathogenesis of glaucoma in MPSs patients was not clear, although a handful of reports explored the pathogenesis.Abnormal accumulation of GAGs may cause glaucoma in MPSs patients by affecting functions and structures of eye, including TM, cornea, ciliary body and sclera. Clinical manifestations and shortened life span could hamper diagnosis of glaucoma in MPSs patients and block knowledge accumulation on the benefits and risks of anti-glaucoma therapies. Despite the fact that cases of glaucoma in MPSs patients were rarely reported, prevalence of glaucoma in MPSs patients (ranged from 2.1% to 12.5%) indicated that glaucoma in MPSs patients was worthy of attention and further study so that quality of life for MPSs patients could be improved.