Projected loss of brown macroalgae and seagrasses with global environmental change.

Although many studies predict extensive future biodiversity loss and redistribution in the terrestrial realm, future changes in marine biodiversity remain relatively unexplored. In this work, we model global shifts in one of the most important marine functional groups-ecosystem-structuring macrophytes-and predict substantial end-of-century change. By modelling the future distribution of 207 brown macroalgae and seagrass species at high temporal and spatial resolution under different climate-change projections, we estimate that by 2100, local macrophyte diversity will decline by 3-4% on average, with 17 to 22% of localities losing at least 10% of their macrophyte species. The current range of macrophytes will be eroded by 5-6%, and highly suitable macrophyte habitat will be substantially reduced globally (78-96%). Global macrophyte habitat will shift among marine regions, with a high potential for expansion in polar regions.

Development of the Escalation of Therapy or Intervention (ETI) Calculator for Patients with Ulcerative Colitis Using ePROMs.

BACKGROUND AND AIMS: Digital collection of patient-reported outcome measures [PROMs] is largely unexplored as a basis for follow-up for patients with ulcerative colitis [UC]. Our aim was to develop a model to predict the likelihood of escalation of therapy or intervention at an outpatient appointment that may be used to rationalize follow-up. METHODS: TrueColours-IBD is a web-based, real-time, remote monitoring software that allows longitudinal collection of ePROMs. Data for prediction modelling were derived from a Development Cohort, guided by the TRIPOD statement. Logistic regression modelling used ten candidate items to predict escalation of therapy or intervention. An Escalation of Therapy or Intervention [ETI] calculator was developed, and applied in a Validation Cohort at the same centre. RESULTS: The Development Cohort [n = 66] was recruited in 2016 and followed for 6 months [208 appointments]. From ten items, four significant predictors of ETI were identified: SCCAI, IBD Control-8, faecal calprotectin, and platelets. For practicality, a model with only SCCAI and IBD Control-8, both entered remotely by the patient, without the need for faecal calprotectin or blood tests was selected. Between 2018 and 2020, a Validation Cohort of 538 patients [1188 appointments] was examined. A 5% threshold on the ETI calculator correctly identified 343/388 [88%] escalations and 274/484 [57%] non-escalations. CONCLUSIONS: A calculator based on digital, patient-entered data on symptoms and quality of life can predict whether a patient with UC requires escalation of therapy or intervention at an outpatient appointment. This may be used to streamline outpatient appointments for patients with UC.

Seasonal and spatial variability in rates of primary production and detritus release by intertidal stands of Laminaria digitata and Saccharina latissima on wave-exposed shores in the northeast Atlantic.

Coastal habitats are increasingly recognized as fundamentally important components of global carbon cycles, but the rates of carbon flow associated with marine macrophytes are not well resolved for many species in many regions. We quantified density, rates of primary productivity, and detritus production of intertidal stands of two common intertidal kelp species-Laminaria digitata (oarweed) and Saccharina latissima (sugar kelp)-on four NE Atlantic rocky shores over 22 months. The density of L. digitata was greater at exposed compared to moderately exposed shores but remained consistently low for S. latissima throughout the survey period. Individual productivity and erosion rates of L. digitata did not differ between exposed and moderately exposed shores but differed across exposure levels throughout the year at moderately exposed sites only. Productivity and erosion of S. latissima remained low on moderately exposed shores and showed no clear seasonal pattern. Patterns of productivity and total detrital production (erosion and dislodgement) per m2 of both L. digitata and S. latissima followed closely that of densities per m2, peaking in May during both survey years. Temperature and light were key factors affecting the productivity rates of L. digitata and S. latissima. Erosion rates of L. digitata were affected by wave exposure, temperature, light, grazing, and epiphyte cover, but only temperature-affected erosion of S. latissima. Production of biomass and detritus was greater in L. digitata than in S. latissima and exceeded previous estimates for subtidal and warmer-water affinity kelp populations (e.g., Laminaria ochroleuca). These biogenic habitats are clearly important contributors to the coastal carbon cycle that have been overlooked previously and should be included in future ecosystem models. Further work is required to determine the areal extent of kelp stands in intertidal and shallow subtidal habitats, which is needed to scale up local production estimates to entire coastlines.

Controlling Cell Trafficking: Addressing Failures in CAR T and NK Cell Therapy of Solid Tumours.

The precision guiding of endogenous or adoptively transferred lymphocytes to the solid tumour mass is obligatory for optimal anti-tumour effects and will improve patient safety. The recognition and elimination of the tumour is best achieved when anti-tumour lymphocytes are proximal to the malignant cells. For example, the regional secretion of soluble factors, cytotoxic granules, and cell-surface molecule interactions are required for the death of tumour cells and the suppression of neovasculature formation, tumour-associated suppressor, or stromal cells. The resistance of individual tumour cell clones to cellular therapy and the hostile environment of the solid tumours is a major challenge to adoptive cell therapy. We review the strategies that could be useful to overcoming insufficient immune cell migration to the tumour cell mass. We argue that existing 'competitive' approaches should now be revisited as complementary approaches to improve CAR T and NK cell therapy.

Intensive multidisciplinary feeding intervention for patients with avoidant/restrictive food intake disorder associated with severe food selectivity: An electronic health record review.

OBJECTIVE: Expert consensus increasingly recognizes intensive multidisciplinary intervention (IMI) as the standard of care to address chronic and severe feeding problems in pediatric populations. In this study, we examined the clinical presentation, intervention characteristics, and treatment outcomes for young children receiving IMI for avoidant restrictive rood intake disorder (ARFID) involving nutritional insufficiencies associated with severe food selectivity. METHOD: We followed the Strengthening the Reporting of Observational Studies in Epidemiology statement to conduct this retrospective chart review. The review focused on consecutive patients (birth to age 21 years) admitted to the IMI program over a 5-year period (June 2014 to June 2019). Inclusion criteria required micronutrient insufficiencies (vitamins A, B12, C, D, E; folic acid; calcium; iron; and zinc) and chronic mealtime refusal behavior (e.g., turning head away from food/spoon, pushing or throwing spoon, crying, screaming, and leaving the table) associated with severe food selectivity. RESULTS: Over the 5-year period, 63 of the patients met study entry requirements. Of these, 60 patients (50 boys and 10 girls; mean age = 72 ± 39 months; range = 23-181) completed intervention (95% treatment completion rate). At discharge, dietary diversity improved by 16 new therapeutic foods (range: 8-22), rapid acceptance and swallowing of new foods exceeded clinical benchmarks (80% or > bites), and risk for nutritional inadequacies declined for this patient cohort. DISCUSSION: Results of the current study support the benefits of IMI to increase dietary variety, improve mealtime behaviors, and enhance nutritional intake for children with ARFID presenting with severe food selectivity.

Individual species provide multifaceted contributions to the stability of ecosystems.

Exploration of the relationship between species diversity and ecological stability has occupied a prominent place in ecological research for decades. Yet, a key component of this puzzle-the contributions of individual species to the overall stability of ecosystems-remains largely unknown. Here, we show that individual species simultaneously stabilize and destabilize ecosystems along different dimensions of stability, and also that their contributions to functional (biomass) and compositional stability are largely independent. By simulating experimentally the extinction of three consumer species (the limpet Patella, the periwinkle Littorina and the topshell Gibbula) from a coastal rocky shore, we found that the capacity to predict the combined contribution of species to stability from the sum of their individual contributions varied among stability dimensions. This implies that the nature of the diversity-stability relationship depends upon the dimension of stability under consideration, and may be additive, synergistic or antagonistic. We conclude that, although the profoundly multifaceted and context-dependent consequences of species loss pose a significant challenge, the predictability of cumulative species contributions to some dimensions of stability provide a way forward for ecologists trying to conserve ecosystems and manage their stability under global change.

Combined effects of warming and nutrients on marine communities are moderated by predators and vary across functional groups.

Warming, nutrient enrichment and biodiversity modification are among the most pervasive components of human-induced global environmental change. We know little about their cumulative effects on ecosystems; however, even though this knowledge is fundamental to predicting and managing their consequences in a changing world. Here, we show that shifts in predator species composition can moderate both the individual and combined effects of warming and nutrient enrichment in marine systems. However, all three aspects of global change also acted independently to alter different functional groups in our flow-through marine rock-pool mesocosms. Specifically, warming reduced macroalgal biomass and assemblage productivity, whereas enrichment led to increased abundance of meso-invertebrate consumers, and loss of predator species led to increased gastropod grazer biomass. This disparity in responses, both across trophic levels (macroalgae and intermediate consumers), and between detecting additive effects on aggregate measures of ecosystem functioning, yet interactive effects on community composition, illustrates that our forecasting ability depends strongly on the level of ecological complexity incorporated within global change experiments. We conclude that biodiversity change-and loss of predator species in particular-plays a critical and overarching role in determining how ecological communities respond to stressors.

Linking marine ecosystems with the services they supply: what are the relevant service providing units?

Marine ecosystems support supply of ecosystem services (ESs) through processes and functions carried out by diverse biological elements. Managing sustainability of ES use requires linking services to the parts of ecosystems supplying them. We specified marine service providing units (SPUs) as plausible combinations of a biotic group (e.g., bacteria, seabirds) with an associated major habitat (e.g., sublittoral sediment). We developed a network model for large marine ecosystems, documenting 2,916 links between 153 SPUs with 31 services. Coastal habitats and their taxa accounted for 48% of links, but all habitats with their taxa contribute to at least 20 ESs. Through network analysis, we showed some services link to certain key habitats, while others are less clearly defined in space, being supported by a variety of habitats and their taxa. Analysis highlighted large-scale flows across marine habitats that are essential in underpinning continued supply of certain ESs, for example, seed dispersal. If we only protect habitats where services are used, we will not fully protect the supply of services reliant on mobile taxa moving between habitats. This emerged because we considered habitats and their taxa together. We recommend using combinations of habitats and taxa as SPUs when informing marine ecosystem management and conservation.

Pronoun Interpretation in the Second Language: Effects of Computational Complexity.

Children acquiring their native language (L1) have been reported to have greater difficulty in interpreting pronouns than reflexives. In addition, they are less accurate when pronouns refer to referential antecedents than to quantified antecedents, and when they hear full pronouns as opposed to reduced pronouns. We hypothesize that similar difficulties of interpretation will occur for (non-advanced) second language (L2) learners, due to an elevated computational burden, as argued for L1 acquisition by Reinhart (2006, 2011). We report on an experiment with adult learners of English (L1s French and Spanish), using a truth-value judgment task. Participants interpreted reduced and full pronouns bound by referential and quantified antecedents in aurally presented test sentences. The learners' performance is affected by type of pronoun and antecedent. When a referential antecedent is combined with a full pronoun, learners' accuracy is significantly lower. These results are in line with Reinhart's analysis of reference set computation in processing pronouns.

Beyond endoscopic mucosal healing in UC: histological remission better predicts corticosteroid use and hospitalisation over 6†years of follow-up.

BACKGROUND: Endoscopic mucosal healing is an established treatment target for UC, yet the value of achieving histological remission remains unclear. AIMS: To evaluate histological remission compared to endoscopic mucosal healing for predicting patient outcomes in UC. METHODS: Blinded assessment of endoscopic and histological measures of disease activity was performed on patients with established UC at baseline. Concordance and prognostic values of endoscopic mucosal healing (defined by Baron score ≤1) and histological remission (defined by Truelove and Richards' index) for predicting outcomes of corticosteroid use, hospitalisation and colectomy were determined over a median 6 years follow-up, including κ statistics and Cox regression multivariate analysis. RESULTS: 91 patients with UC were followed up for a median 72 months (IQR 54-75 months). Overall, concordance between endoscopic and histological remission was moderate (κ=0.56, 95% CI 0.36 to 0.77); 24% patients had persistent inflammation despite endoscopic remission. Histological remission predicted corticosteroid use and acute severe colitis requiring hospitalisation over the follow-up period (HR 0.42 (0.2 to 0.9), p=0.02; HR 0.21 (0.1 to 0.7), p=0.02; respectively), whereas endoscopic mucosal healing did not (HR 0.86, 95% CI 0.5 to 1.7, p0.65; HR 0.83 95% CI 0.3 to 2.4, p0.74; respectively). CONCLUSIONS: Histological remission is a target distinct from endoscopic mucosal healing in UC and better predicts lower rates of corticosteroid use and acute severe colitis requiring hospitalisation, over a median of 6 years of follow-up. Our findings support the inclusion of histological indices in both UC clinical trials and practice, towards a target of 'complete remission'.

Association between the ulcerative colitis endoscopic index of severity (UCEIS) and outcomes in acute severe ulcerative colitis.

BACKGROUND: The Ulcerative Colitis Endoscopic Index of Severity (UCEIS) accounts for 86% of the variance between observers in the overall assessment of endoscopic severity, but has not been correlated with outcomes. METHODS: Consecutive cases of acute severe colitis (ASC) defined by Truelove and Witts (TW) criteria were retrospectively evaluated. Demographic details, number of TW criteria, prior medical therapy, UCEIS and inpatient medical therapy were recorded. Pre-specified (adverse) endpoints included rescue therapy, colectomy and readmission. RESULTS: Eighty-nine patients, 48 (54%) male, mean age 38 years, all received intravenous hydrocortisone 400mg/d (median 5 days [range 1-11]). Median follow-up was 14 months (2-33). Forty-eight (54%) were diagnosed the year prior to or at the time of admission. Thirty-six (40%) required rescue therapy (infliximab 25/36, ciclosporin 12/36, one receiving both). Twenty-one (24%) underwent colectomy on the index admission (9/21) or during follow-up (12/21). Median UCEIS score (possible range 0-8) was 5 (3-8). UCEIS was higher in patients requiring rescue therapy or colectomy (median score 6 [range 4-8] versus 5/8 [3-8], both p < 0.005). For UCEIS ≥5, 27/54 (50%) required rescue therapy, compared with 9/33 (27%) for UCEIS ≤4 (p = 0.037). When UCEIS was ≥5, 18/54 (33%) came to colectomy during follow-up, compared with 3/33 (9%) with UCEIS ≤4. Of 14 patients with UCEIS 7 or 8, 11/14 needed rescue therapy and 13/14 met any adverse endpoint. CONCLUSION: Endoscopic severity is associated with a worse outcome in ASC. When the UCEIS is ≥7 on admission, almost all patients will need treatment with infliximab or ciclosporin beyond steroids. This may mark a threshold for an early decision to use infliximab or ciclosporin.

Perfused, pulseless, and puzzling: a systematic review of vascular injuries in pediatric supracondylar humerus fractures and results of a POSNA questionnaire.

BACKGROUND: Supracondylar humerus fractures that present with a perfused, viable hand yet no pulse continue to be a source of controversy. The purpose of this study was to conduct a systematic review of the literature and perform a Pediatric Orthopaedic Society of North America (POSNA) opinion poll regarding management of pulseless supracondylar humeral fractures in children. METHODS: A systematic review of the literature was conducted for relevant observational studies concerning neurovascular injuries in supracondylar humerus fractures. Single case reports and non-English language studies were excluded. Data were pooled for defined subgroups and 95% confidence intervals were reported. The results from the literature were then compared to popular opinion via a POSNA-approved survey concerning management of pulseless supracondylar humerus fractures. RESULTS: A total of 331 cases of pulseless supracondylar fractures were identified from the literature, irrespective of perfusion status. In all, 157 fractures remained pulseless after closed reduction and stabilization. Of the fractures that continued to be pulseless despite adequate reduction, 82% [95% confidence interval (CI)=0.82 (0.76-0.88)] were found to have a documented brachial artery injury. POSNA members presumed this number would be 28% [95% CI=0.28 (0.22-0.34)]. A total of 98 perfused (aka pink) supracondylar fractures were identified. Of these pulseless, perfused fractures, 70% [95% CI=0.70 (0.58-0.82)] had a documented brachial artery injury. POSNA members speculated that this number would be 17% [95% CI=0.17 (0.12-0.22). A total of 54 patients had minimum 1 year follow-up data after vascular revascularization, and 91% [95% CI=0.91 (0.83-0.99)] of these patients had a patent artery based on vascular studies. POSNA members believed this number would be 55% [95% CI=0.55 (0.48-0.62)]. CONCLUSIONS: Our study revealed that common dogma regarding watchful waiting of pulseless and perfused supracondylar fractures needs to be questioned. In the vast majority of published cases, an absence of pulse is an indicator of arterial injury, even if the hand appears pink and warm, suggesting the need for more aggressive vascular evalvation and vascular exploration and repair in selected cases. Moreover, patency rates for revascularization procedures appear sufficiently high, making this intervention worthwhile.

Palmar dislocation of the trapezoid with coronal shearing fracture: case report.

We report an unusual variant of a palmar trapezoid dislocation with a shearing fracture of the dorsal cortex treated with mini-fragment screw fixation. This patient's treatment is compared to the few previously published reports of palmarly dislocated trapezoids to assist hand surgeons facing this uncommon injury.

Selective serotonin reuptake inhibitors (SSRIs) and routine specialist care with and without cognitive behaviour therapy in adolescents with major depression: randomised controlled trial.

OBJECTIVE: To determine whether a combination of a selective serotonin reuptake inhibitor (SSRIs) and cognitive behaviour therapy (CBT) together with clinical care is more effective in the short term than an SSRI and clinical care alone in adolescents with moderate to severe major depression. DESIGN: Pragmatic randomised controlled superiority trial. SETTING: 6 outpatient clinics in Manchester and Cambridge. PARTICIPANTS: 208 adolescents, aged 11-17, with moderate to severe major or probable major depression who had not responded to a brief initial intervention. Adolescents with suicidality, depressive psychosis, or conduct disorder were included. INTERVENTIONS: 103 adolescents received an SSRI and routine care; 105 received an SSRI, routine care, and CBT. The trial lasted 12 weeks, followed by a 16 week maintenance phase. MAIN OUTCOME MEASURES: Change in score on the Health of the Nation outcome scales for children and adolescents (primary outcome) from baseline with 12 weeks as the primary and 28 weeks as the follow-up end point. Secondary measures were change in scores on the mood and feelings questionnaire, the revised children's depression rating scale, the children's global assessment scale, and the clinical global impression improvement scale. RESULTS: At 12 weeks the treatment effect for the primary outcome was -0.64 (95% confidence interval -2.54 to 1.26, P=0.50). In a longitudinal analysis, there was no difference in effectiveness of treatment for the primary (average treatment effect 0.001, -1.52 to 1.52, P=0.99) or secondary outcome measures. On average there was a decrease in suicidal thoughts and self harm. There was no evidence of a protective effect of cognitive behaviour therapy on suicidal thinking or action. By 28 weeks, 57% were much or very much improved with 20% remaining unimproved. CONCLUSIONS: For adolescents with moderate to severe major depression there is no evidence that the combination of CBT plus an SSRI in the presence of routine clinical care contributes to an improved outcome by 28 weeks compared with the provision of routine clinical care plus an SSRI alone. TRIAL REGISTRATION: Current Controlled Trials ISRCNT 83809224.