ALK-positive histiocytosis: a new clinicopathologic spectrum highlighting neurologic involvement and responses to ALK inhibition.

ALK-positive histiocytosis is a rare subtype of histiocytic neoplasm first described in 2008 in 3 infants with multisystemic disease involving the liver and hematopoietic system. This entity has subsequently been documented in case reports and series to occupy a wider clinicopathologic spectrum with recurrent KIF5B-ALK fusions. The full clinicopathologic and molecular spectra of ALK-positive histiocytosis remain, however, poorly characterized. Here, we describe the largest study of ALK-positive histiocytosis to date, with detailed clinicopathologic data of 39 cases, including 37 cases with confirmed ALK rearrangements. The clinical spectrum comprised distinct clinical phenotypic groups: infants with multisystemic disease with liver and hematopoietic involvement, as originally described (Group 1A: 6/39), other patients with multisystemic disease (Group 1B: 10/39), and patients with single-system disease (Group 2: 23/39). Nineteen patients of the entire cohort (49%) had neurologic involvement (7 and 12 from Groups 1B and 2, respectively). Histology included classic xanthogranuloma features in almost one-third of cases, whereas the majority displayed a more densely cellular, monomorphic appearance without lipidized histiocytes but sometimes more spindled or epithelioid morphology. Neoplastic histiocytes were positive for macrophage markers and often conferred strong expression of phosphorylated extracellular signal-regulated kinase, confirming MAPK pathway activation. KIF5B-ALK fusions were detected in 27 patients, whereas CLTC-ALK, TPM3-ALK, TFG-ALK, EML4-ALK, and DCTN1-ALK fusions were identified in single cases. Robust and durable responses were observed in 11/11 patients treated with ALK inhibition, 10 with neurologic involvement. This study presents the existing clinicopathologic and molecular landscape of ALK-positive histiocytosis and provides guidance for the clinical management of this emerging histiocytic entity.

A decision support procedure for the bioeconomy transition: A Colombian case study.

An increasing number of countries and regions consider the bioeconomy transition a strategic policy priority. When approached through the lens of a circular economy perspective, investments in bioeconomy have the potential to enhance resource utilisation efficiency, preserve biodiversity and ecosystems, and foster sustainable development with low emissions. At the same time, if requirements and contextual factors of bioeconomy strategies are not formally analysed, bioeconomic investments might lead to unintended negative consequences. This paper proposes a decision support procedure to design, assess, prioritise, and monitor bioeconomy investments and policies. The flexibility and scalability of our decision support procedure is tested in Colombia to foster a regional and local transition to bioeconomy initiatives that consider the local capital assets and the stakeholders' views. The heterogeneous character of the Colombian environment, economy, society and culture represents an ideal condition to test the strength of the decision support procedure to promote bioeconomy in low and middle-income countries. Our empirical results highlight the benefit of adopting a formal assessment framework that includes strategic national indicators, regional features and stakeholders' views. In terms of the Colombian regional bioeconomy ambitions, we highlight the need for expanding knowledge hubs and participatory stakeholder networks and buttressing appropriate financial mechanisms.

Ecosystem health, ecosystem services, and the well-being of humans and the rest of nature.

An ecosystem is healthy if it is active, maintains its organization and autonomy over time, and is resilient to stress. Healthy ecosystems provide human well-being via ecosystem services, which are produced in interaction with human, social, and built capital. These services are affected by different ecosystem stewardship schemes. Therefore, society should be aiming for ecosystem health stewardship at all levels to maintain and improve ecosystem services. We review the relationship between ecosystem health and ecosystem services, based on a logic chain framework starting with (1) a development or conservation policy, (2) a management decision or origin of the driver of change, (3) the driver of change itself, (4) the change in ecosystem health, (5) the change in the provision of ecosystem services, and (6) the change in their value to humans. We review two case studies to demonstrate the application of this framework. We analyzed 6,131 records from the Ecosystem Services Valuation Database (ESVD) and found that in approximately 58% of the records data on ecosystem health were lacking. Finally, we describe how the United Nations' System of Environmental-Economic Accounting (SEEA) incorporates ecosystem health as part of efforts to account for natural capital appreciation or depreciation at the national level. We also provide recommendations for improving this system.

Paediatric inflammatory multisystem syndrome: temporally associated with SARS-CoV-2 (PIMS-TS) - A mimic of intra-abdominal malignancy.

We report the case of a school-aged boy who presented with clinical features suggesting acute appendicitis. However, further imaging which included CT, demonstrated an inflammatory mass involving the transverse colon raising the suspicion of lymphoma. He then developed intestinal obstruction, and in view of the rapid progression of the disease, he was thought to have non-Hodgkin's lymphoma. He underwent an open excisional biopsy, which revealed a necroinflammatory process and no suggestion of lymphoma or an alternative malignancy or specific diagnosis. His steroid treatment was stopped, and he made a good recovery postoperatively. Positive COVID-19 antibodies, positive response to steroids, results and clinical features were consistent with paediatric inflammatory multisystem syndrome (PIMS-TS), with extensive investigation not offering an alternative diagnosis.While PIMS-TS is a relatively new entity, we believe that this case highlights the importance of it being considered a differential diagnosis of a child presenting with an inflammatory mass.

SARS-COV2 placentitis and pregnancy outcome: A multicentre experience during the Alpha and early Delta waves of coronavirus pandemic in England.

Background: Pregnant women with SARS-CoV-2 infection experience higher rates of stillbirth and preterm birth. A unique pattern of chronic histiocytic intervillositis (CHI) and/or massive perivillous fibrin deposition (MPFD) has emerged, coined as SARS-CoV-2 placentitis. Methods: The aim of this study was to describe a cohort of placentas diagnosed with SARS-CoV-2 placentitis during October 2020-March 2021. Cases with a histological diagnosis of SARS-CoV-2 placentitis and confirmatory immunohistochemistry were reported. Maternal demographic data, pregnancy outcomes and placental findings were collected. Findings: 59 mothers delivered 61 infants with SARS-CoV-2 placentitis. The gestational age ranged from 19 to 41 weeks with most cases (78.6%) being third trimester. 30 infants (49.1%) were stillborn or late miscarriages. Obese mothers had higher rates of pregnancy loss when compared with those with a BMI <30 [67% (10/15) versus 41% (14/34)]. 47/59 (79.7%) mothers had a positive SARS-CoV-2 PCR test either at the time of labour or in the months before, of which 12 (25.5%) were reported to be asymptomatic. Ten reported only CHI, two cases showed MPFD only and in 48 placentas both CHI and MPFD was described. Interpretation: SARS-CoV2 placentitis is a distinct entity associated with increased risk of pregnancy loss, particularly in the third trimester. Women can be completely asymptomatic and still experience severe placentitis. Unlike 'classical' MPFD, placentas with SARS-CoV-2 are generally normal in size with adequate fetoplacental weight ratios. Further work should establish the significance of the timing of maternal SARS-CoV-2 infection and placentitis, the significance of SARS-CoV2 variants, and rates of vertical transmission associated with this pattern of placental inflammation. Funding: There was not funding associated with this study.

Histopathology of laryngomalacia.

BACKGROUND: Laryngomalacia is the commonest laryngeal anomaly and cause of stridor in children. Although most cases are self-limiting, failure to thrive, hypoxaemia or significant apnoeic episodes may warrant surgical intervention in the form of aryepiglottoplasty. Opinion is divided as to the pathophysiological mechanisms involved in the disease process. AIMS AND OBJECTIVES: This study explores the aetiology of laryngomalacia by reviewing the histology of aryepiglottoplasty resection specimens. MATERIAL AND METHODS: The histology reports of 61 aryepiglottoplasty specimens resected between 1 October 2014 and 31 October 2018 were reviewed. RESULTS: Age of patients ranged from 3 weeks to 36 months. 36 patients were male and 25 female. 43 of 61 (70.5%) cases had inflammation, most of which were mild. 3 (4.9%) cases had histological specimens with detectable eosinophils. None of the specimens had signs of granulomatous change, ulceration or calcification. Cartilage was present in the resected specimen in 47 (77%) cases. Over half of these (59.6%) were immature cartilage. CONCLUSION AND SIGNIFICANCE: The results suggest a mild concurrent laryngitis/supraglottitis in most cases. Eosinophilia is rare and does not support eosinophilic oesophageal reflux as part of the aetiology. The high proportion of immature cartilage in the specimens supports the theory of chondropathic aetiology.

Management of pediatric benign ovarian tumors in England and Egypt: A comparative study.

AIM OF THE STUDY: We aimed to compare the management of pediatric benign ovarian tumors between an English center and three Egyptian institutions. MATERIALS AND METHODS: This was a retrospective review of all children presenting with benign ovarian tumors between January 2014 and January 2019. A standardized dataset was used to compare between both sides. RESULTS: Eighty-nine patients were included (54 English and 35 Egyptians). Median age at diagnosis in England was 13 years (2-16y), while in Egypt it was 7 years (9m-16y) with P =0.001. Mature teratomas or dermoid cysts were the most common findings in England and Egypt; 75.9% and 82.8% of cases, respectively. The presentation with an acute abdomen represented 27.8% of English and 28.6% of Egyptian patients. Incidentally diagnosed lesions constituted 15% of English patients, whereas none of the Egyptian cases were discovered incidentally. There were variations in diagnostic imaging; England: Ultrasound (USS) (54), magnetic resonance imaging (MRI) (37), and computed tomography (CT) (only one)-Egypt: USS (35), CT (17), and MRI (only one). Minimally invasive surgery (MIS) was performed in 15% of English and 23% of Egyptian patients (P = 0.334). Ovarian-sparing surgery (OSS) was performed in: England 35%, Egypt 37%; P = 0.851. OSS was performed using MIS in 87.5% (7/8) of English patients and 100% (8/8) of Egyptians. Patients presented as emergencies generally had open oophorectomies: England; 86.7% open and 80% oophorectomy-Egypt; 100% open and 90% oophorectomy. Recurrences or metachronous disease occurred in 5.6% of English and 5.7% of Egyptian patients. CONCLUSIONS: There were no significant differences regarding surgical management, tumor pathology, and recurrence or metachronous disease. However, age, incidental diagnosis, and imaging modalities showed notable differences. MIS was correlated with ovarian preservation, whereas emergency surgery generally resulted in open oophorectomy.

Ecosystem services and economic theory: integration for policy-relevant research.

It has become essential in policy and decision-making circles to think about the economic benefits (in addition to moral and scientific motivations) humans derive from well-functioning ecosystems. The concept of ecosystem services has been developed to address this link between ecosystems and human welfare. Since policy decisions are often evaluated through cost-benefit assessments, an economic analysis can help make ecosystem service research operational. In this paper we provide some simple economic analyses to discuss key concepts involved in formalizing ecosystem service research. These include the distinction between services and benefits, understanding the importance of marginal ecosystem changes, formalizing the idea of a safe minimum standard for ecosystem service provision, and discussing how to capture the public benefits of ecosystem services. We discuss how the integration of economic concepts and ecosystem services can provide policy and decision makers with a fuller spectrum of information for making conservation-conversion trade-offs. We include the results from a survey of the literature and a questionnaire of researchers regarding how ecosystem service research can be integrated into the policy process. We feel this discussion of economic concepts will be a practical aid for ecosystem service research to become more immediately policy relevant.

Nontraumatic intradural and subdural hemorrhage and hypoxic ischemic encephalopathy in fetuses, infants, and children up to three years of age: analysis of two audits of 636 cases from two referral centers in the United Kingdom.

We analyzed the presence or absence of intradural hemorrhage (IDH) and subdural hemorrhage (SDH) and the degree of hypoxic-ischemic encephalopathy (HIE) in the brain of all nonmacerated fetuses of >24 weeks, neonates, and children up to 3 years of age who died of natural causes over a defined period. We looked into the cause of death and the performance of cardiopulmonary resuscitation in our cohort. The IDH was classified as macroscopic or negative/microscopic only; the HIE was classified as absent, indeterminate, or definite. In fetuses, SDH with IDH was present in 22%; IDH alone was present in 31%, and there was no or minimal hemorrhage in 47% of cases. In infants and children SDH with IDH was present in 19%; IDH alone was present in the 32%, and there was no or minimal hemorrhage in 49% of cases. There was a statistically significant correlation between SDH and HIE, especially in infants and children (P < 0.001). When cases were grouped per age, a significant association between age and hemorrhage (P < 0.0001) was demonstrated, SDH being more common in infants ≤1 month corrected age. Intradural hemorrhage can be the source of thin-film SDH in fetuses, infants, and young children. The presence of SDH is associated with hypoxia. Intradural and subdural hemorrhages are more common in autopsies of infants under 1 month corrected age. Although more rare, they can also be found in children between 1 month and 3 years of age in the absence of trauma.

Can the benefits of physical seabed restoration justify the costs? An assessment of a disused aggregate extraction site off the Thames Estuary, UK.

Physical and biological seabed impacts can persist long after the cessation of marine aggregate dredging. Whilst small-scale experimental studies have shown that it may be possible to mitigate such impacts, it is unclear whether the costs of restoration are justified on an industrial scale. Here we explore this question using a case study off the Thames Estuary, UK. By understanding the nature and scale of persistent impacts, we identify possible techniques to restore the physical properties of the seabed, and the costs and the likelihood of success. An analysis of the ecosystem services and goods/benefits produced by the site is used to determine whether intervention is justified. Whilst a comparison of costs and benefits at this site suggests restoration would not be warranted, the analysis is site-specific. We emphasise the need to better define what is, and is not, an acceptable seabed condition post-dredging.

The market triumph of ecotourism: an economic investigation of the private and social benefits of competing land uses in the Peruvian Amazon.

Annual revenue flow to developing countries for ecotourism (or nature-based tourism) could be as large as US$ 210×10(12), providing an enormous financial incentive against habitat loss and exploitation. However, is ecotourism the most privately and/or socially valuable use of rainforest land? The question is rarely answered because the relevant data, estimates of profits and fixed costs, are rarely available. We present a social cost-benefit analysis of land use in an ecotourism cluster in the Tambopata region of Amazonian Peru. The net present value of ecotourism-controlled land is given by the producer surplus (profits plus fixed costs of ecotourism lodges): US$ 1,158 ha(-1), which is higher than all currently practiced alternatives, including unsustainable logging, ranching, and agriculture. To our knowledge, this is the first sector-wide study of profitability and producer surplus in a developing-country ecotourism sector and the first to compare against equivalent measures for a spectrum of alternative uses. We also find that ecotourism-controlled land sequesters between 5.3 to 8.7 million tons of above-ground carbon, which is equivalent to between 3000-5000 years of carbon emissions from the domestic component of air and surface travel between the gateway city of Cusco and the lodges, at 2005 emission rates. Ecotourism in Tambopata has successfully monetized the hedonic value of wild nature in Amazonian Peru, and justifies the maintenance of intact rainforest over all alternative uses on narrow economic grounds alone.

Impact of 100-year human interventions on the deltaic coastal zone of the Inner Thermaikos Gulf (Greece): a DPSIR framework analysis.

The Axios River delta and the Inner Thermaikos Gulf coastal zone have experienced a long period of human interventions during the past 100 years. A post-evaluation of long run coastal zone changes under the Drivers-Pressures-State-Impacts-Response (DPSIR) conceptual framework is presented. The DPSIR approach is then used to project out into possible futures in order to connect with policy and management options proposed for the improvement of the current conditions and the achievement of sustainable development, in the coastal zone. Socio-economic driving forces with their origins in the end of the 19th century have generated numerous pressures in the coastal environment that changed the state of the environment. In the first part of the last century, there was no coupling between change of state and policy. Due to increasing environmental awareness, a coupling became more apparent over the last thirty years. Human interventions include river route realignment, extensive drainage of the plains, irrigation network, roads and dam constructions. The consequences were positive for the economic development of the area, human health, and navigation for the port of Thessaloniki. In contrast, the manipulation and over-use of natural resources has led to a reduction of wetlands, biodiversity loss, stress on freshwater supplies, and subsidence of coastal areas, aquifer salinization, and rapid coastal erosion. Three plausible future scenarios are utilised in order to investigate the implications of this environmental change process and possible socio-economic consequences.