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ContextUnderstanding how the Northern Forest landscape has changed and is likely to change, both in terms of forest extent and forest configuration, has important implications for management.ObjectivesWe examined historical changes in forest pattern and extent to: (1) characterize recent forest cover change and potential drivers of that change, (2) identify areas vulnerable to future forest loss, (3) assess the impact of such loss on forest fragmentation, and (4) examine correlations between projected forest loss and socioeconomic variables to help inform future planning.MethodsWe developed a cellular automata model to simulate changes in forest land cover in the Northern Forest region from 2015 to 2075. The model was parameterized from observed historical trends (1985 to 2015) and correlating spatial variables using Bayesian Weights of Evidence. Using our model outputs, we identified areas most vulnerable to change, and impacts of these changes on forest fragmentation.ResultsThough we find an overall trend of decreasing forest area across the region, rates of change vary spatially and temporally, with an overall increase in forest cover between 2000 and 2015. Areas most attractive for development (e.g. high population density, low slope and elevation) were most likely to experience deforestation. Forest fragmentation increased during observed and simulated time steps, even during an observed period of net forest regeneration.ConclusionsForest loss and fragmentation due to development represent a formidable threat to the Northern Forest. Historical trends indicate that simply increasing forest extent is not sufficient to restore forest connectivity in the region.

Cultural ecosystem services (CES) are some of the most difficult ecosystem services (ES) to characterize and connect to specific ecosystem processes. Given their connections to human emotion, deep meaning, fulfilment and motivation, they are also crucial for human well‐being. Scholars have published hundreds of peer‐reviewed articles addressing CES in myriad ways. In this systematic review, we analyse 232 peer‐reviewed articles on CES and examine how these studies discuss the interaction between CES research and decision‐making. We describe the primary ways that scholars have addressed the relationship between CES and decision‐making, and we characterize each study with respect to how thoroughly its authors attend to the possible applications of their results. We find that 27% of papers discuss connections to decision‐making in general terms, 28% discuss specific connections to decision‐making, and the remainder mention decision‐making links briefly or not at all. We also discuss patterns based on the particular CES studied (e.g. recreation, identity); methods used; change through time; and geographical location of authors and of study sites. We end with reflections on the current state of the interface between CES (and related concepts for approaching the non‐material values associated with ecosystems) and decision‐making, and we discuss future steps to increase connections between CES and decision‐making. A free Plain Language Summary can be found within the Supporting Information of this article. A free Plain Language Summary can be found within the Supporting Information of this article.

PurposeAccurately assessing forest carbon storage on a landscape scale is critical to understanding global carbon cycles and the effects of land cover changes on ecological processes. Calculations of regional-scale forest carbon storage that rely on maps of land cover typically reflect only coarse forest classes. How differences in carbon stored by different tree species may affect such assessments is largely unexplored. We examined a range of forest carbon storage models to understand the effects of forest type specificity on carbon storage estimates in the northeastern United States.MethodsModels estimated forest carbon in total aboveground and coarse root biomass based on three levels of forest classification specificity: (1) relative basal area by species, (2) species associations, and (3) broad forest types per IPCC (in: IPCC guidelines for national greenhouse gas inventories, IPCC, Japan, 2006) guidelines.ResultsThe specificity of forest type classifications influenced results with generally lower carbon storage estimates resulting from higher-specificity forest classifications. The two most specific models, with mean carbon storage estimates of 103–107 Mg/ha, were most accurate compared to field validation points. These estimates are greater than 2013 field-based U.S. Forest Service estimates (84–90 Mg/ha).ConclusionsThere are many sources of uncertainty in landscape-scale carbon storage assessments. Here we show that improving detail in one of these sources, forest stand composition, increases the accuracy of these assessments, and better reflects carbon storage patterns across heterogeneous landscapes. While more work is needed, particularly to improve stand age maps, this information can inform the interpretation of current carbon storage estimates and improve future estimates in heterogeneous forests.

Traditional flood risk paradigms and associated strategies are no longer sufficient to address global flood adaptation challenges due to climate change and continued development in floodplains. The current flood adaptation approach is failing to take advantage of the benefits provided by intact ecosystems and perpetuates social and economic inequities, leaving those who are most vulnerable at highest risk. Rooted in the experiences of the United States, we propose a new framework, the Flood Adaptation Hierarchy, which prioritizes outcomes into six tiers. Overall, the tiers distinguish between nature and nature-based solutions, with preference given to natural ecosystems. The most important outcome in our hierarchy is to avoid risk by protecting and restoring natural floodplains; next, eliminate risk by moving communities away from danger; and then to accommodate water with passive measures and active risk reduction measures. We include, but deprioritize, a defense of community assets using nature-based engineering and hardened engineering. Throughout the hierarchy, we provide guidance on the equity considerations of flood adaptation decision making and highlight “impacts,” “resources,” and “voices” as important equity dimensions. Implementing the framework through an iterative process, using justification criteria to manage movement among tiers, alongside equity considerations, will support adaptation to changing environmental and social conditions and contribute to risk reduction at scale. Though this approach is focused on U.S. flood management and adaptation, prioritizing risk reduction, elimination of risk, and accommodation of hazards over the defense against threats not only has global applicability to flood adaptation, but should also be evaluated for applicability to other climate-driven challenges.

The medical needs of older people are growing because the proportion of the older population is increasing and disease boundaries are widening. This study describes the distribution and clustering of 15 common clinical disorders requiring medical treatment or supervision in a representative British cohort approaching retirement, and how health tracked across adulthood. The data come from a cohort of 2661 men and women, 84% of the target sample, followed since birth in England, Scotland and Wales in 1946, and assessed at 60-64 years for: cardio and cerebro-vascular disease, hypertension, raised cholesterol, renal impairment, diabetes, obesity, hypothyroidism, hyperthyroidism, anaemia, respiratory disease, liver disease, psychiatric problems, cancers, atrial fibrillation on ECG and osteoporosis. We calculated the proportions disorder-free, with one or more disorders, and the level of undiagnosed disorders; and how these disorders cluster into latent classes and relate to health assessed at 36 years. Participants had, on average, two disorders (range 0-9); only 15% were disorder-free. The commonest disorders were hypertension (54.3%, 95% CI 51.8%-56.7%), obesity (31.1%, 28.8%-33.5%), raised cholesterol (25.6%, 23.1-28.26%), and diabetes or impaired fasting glucose (25.0%, 22.6-27.5%). A cluster of one in five individuals had a high probability of cardio-metabolic disorders and were twice as likely than others to have been in the poorest health at 36 years. The main limitations are that the native born sample is entirely white, and a combination of clinical assessments and self reports were used. Most British people reaching retirement already have clinical disorders requiring medical supervision. Widening disease definitions and the move from a disease-based to a risk-based medical model will increase pressure on health services. The promotion of healthy ageing should start earlier in life and consider the individual's ability to adapt to and self manage changes in health.

Background Postoperative pulmonary complications (PPCs) are associated with poor outcomes following thoracotomy and lung resection. Video-assisted thoracoscopic surgery (VATS) for lobectomy is now frequently utilised as an alternative to thoracotomy, however patients remain at risk for development of PPC. There is little known of the short-term outcome associated with PPC following VATS lobectomy and if there are any potential risk factors that could be modified to prevent PPC development; our study aimed to investigate this. Methods A prospective observational study of consecutive patients undergoing VATS lobectomy for lung cancer over a 4-year period in a regional centre was performed (2012–2016). Exclusion criteria included re-do VATS or surgery for pulmonary infection. All patients received physiotherapy as necessary from postoperative day 1 (POD1) and PPC was determined using the Melbourne Group Scale. Outcomes included hospital LOS, intensive therapy unit (ITU) admission and hospital mortality. Results Of the 285 patients included in the study, 137 were male (48.1%), the median (IQR) age was 69 (13) years and the mean (±SD) FEV 1 % predicted was 87% (±19). Patients that developed a PPC ( n  = 21; 7.4%) had a significantly longer hospital LOS (4 vs. 3 days), higher frequency of ITU admission (23.8% vs. 0.5%) and higher hospital mortality (14.3% vs. 0%) ( p  < 0.001). PPC patients also required more physiotherapy contacts/time, emergency call-outs and specific pulmonary therapy ( p  < 0.05). Current smoking and COPD diagnosis were significantly associated with development of PPC on univariate analysis ( p  < 0.05), however only current smoking was a significant independent risk factor on multivariate analysis ( p  = 0.015). Conclusions Patients undergoing VATS lobectomy remain at risk of developing a PPC, which is associated with an increase in physiotherapy requirements and a worse short-term morbidity and mortality. Current smoking is the only independent risk factor for PPC after VATS lobectomy, thus vigorous addressing of preoperative smoking cessation is urgently needed.

Metabolic dyslipidemia is characterized by high circulating triglyceride (TG) and low HDL cholesterol levels and is frequently accompanied by hepatic steatosis. Increased hepatic lipogenesis contributes to both of these problems. Because insulin fails to suppress gluconeogenesis but continues to stimulate lipogenesis in both obese and lipodystrophic insulin-resistant mice, it has been proposed that a selective postreceptor defect in hepatic insulin action is central to the pathogenesis of fatty liver and hypertriglyceridemia in these mice. Here we show that humans with generalized insulin resistance caused by either mutations in the insulin receptor gene or inhibitory antibodies specific for the insulin receptor uniformly exhibited low serum TG and normal HDL cholesterol levels. This was due at least in part to surprisingly low rates of de novo lipogenesis and was associated with low liver fat content and the production of TG-depleted VLDL cholesterol particles. In contrast, humans with a selective postreceptor defect in AKT2 manifest increased lipogenesis, elevated liver fat content, TG-enriched VLDL, hypertriglyceridemia, and low HDL cholesterol levels. People with lipodystrophy, a disorder characterized by particularly severe insulin resistance and dyslipidemia, demonstrated similar abnormalities. Collectively these data from humans with molecularly characterized forms of insulin resistance suggest that partial postreceptor hepatic insulin resistance is a key element in the development of metabolic dyslipidemia and hepatic steatosis.

Phosphatidylcholine (PC) is the major glycerophospholipid in eukaryotic cells and is an essential component in all cellular membranes. The biochemistry of de novo PC synthesis by the Kennedy pathway is well established, but less is known about the physiological functions of PC. We identified two unrelated patients with defects in the Kennedy pathway due to biallellic loss-of-function mutations in phosphate cytidylyltransferase 1 alpha (PCYT1A), the rate-limiting enzyme in this pathway. The mutations lead to a marked reduction in PCYT1A expression and PC synthesis. The phenotypic consequences include some features, such as severe fatty liver and low HDL cholesterol levels, that are predicted by the results of previously reported liver-specific deletion of murine Pcyt1a . Both patients also had lipodystrophy, severe insulin resistance, and diabetes, providing evidence for an additional and essential role for PCYT1A-generated PC in the normal function of white adipose tissue and insulin action.

BackgroundWe aimed for a comprehensive delineation of genetic, functional and phenotypic aspects of GRIN2B encephalopathy and explored potential prospects of personalised medicine.MethodsData of 48 individuals with de novo GRIN2B variants were collected from several diagnostic and research cohorts, as well as from 43 patients from the literature. Functional consequences and response to memantine treatment were investigated in vitro and eventually translated into patient care.ResultsOverall, de novo variants in 86 patients were classified as pathogenic/likely pathogenic. Patients presented with neurodevelopmental disorders and a spectrum of hypotonia, movement disorder, cortical visual impairment, cerebral volume loss and epilepsy. Six patients presented with a consistent malformation of cortical development (MCD) intermediate between tubulinopathies and polymicrogyria. Missense variants cluster in transmembrane segments and ligand-binding sites. Functional consequences of variants were diverse, revealing various potential gain-of-function and loss-of-function mechanisms and a retained sensitivity to the use-dependent blocker memantine. However, an objectifiable beneficial treatment response in the respective patients still remains to be demonstrated.ConclusionsIn addition to previously known features of intellectual disability, epilepsy and autism, we found evidence that GRIN2B encephalopathy is also frequently associated with movement disorder, cortical visual impairment and MCD revealing novel phenotypic consequences of channelopathies.

We present an expanded data set of 50 unlinked autosomal noncoding regions, resequenced in samples of Hausa from Cameroon, Italians, and Chinese. We use these data to make inferences about human demographic history by using a technique that combines multiple aspects of genetic data, including levels of polymorphism, the allele frequency spectrum, and linkage disequilibrium. We explore an extensive range of demographic parameters and demonstrate that our method of combining multiple aspects of the data results in a significant reduction of the compatible parameter space. In agreement with previous reports, we find that the Hausa data are compatible with demographic equilibrium as well as a set of recent population expansion models. In contrast to the Hausa, when multiple aspects of the data are considered jointly, the non-Africans depart from an equilibrium model of constant population size and are compatible with a range of simple bottleneck models, including a 50-90% reduction in effective population size occurring some time after the appearance of modern humans in Africa 160,000-120,000 years ago.