Land surface conductance linked to precipitation: Co-evolution of vegetation and climate in Earth system models.

Vegetation and precipitation are known to fundamentally influence each other. However, this interdependence is not fully represented in climate models because the characteristics of land surface (canopy) conductance to water vapor and CO2 are determined independently of precipitation. Working within a coupled atmosphere and land modelling framework (CAM6/CLM5; coupled Community Atmosphere Model v6/Community Land Model v5), we have developed a new theoretical approach to characterizing land surface conductance by explicitly linking its dynamic properties to local precipitation, a robust proxy for moisture available to vegetation. This will enable regional surface conductance characteristics to shift fluidly with climate change in simulations, consistent with general principles of co-evolution of vegetation and climate. Testing within the CAM6/CLM5 framework shows that climate simulations incorporating the new theory outperform current default configurations across several error metrics for core output variables when measured against observational data. In climate simulations for the end of this century the new, adaptive stomatal conductance scheme provides a revised prognosis for average and extreme temperatures over several large regions, with increased primary productivity through central and east Asia, and higher rainfall through North Africa and the Middle East. The new projections also reveal more frequent heatwaves than originally estimated for the south-eastern US and sub-Saharan Africa but less frequent heatwaves across east Europe and northeast Asia. These developments have implications for evaluating food security and risks from extreme temperatures in areas that are vulnerable to climate change.

Factors associated with cellulitis in lymphoedema of the arm - an international cross-sectional study (LIMPRINT).

BACKGROUND: Lymphoedema is a globally neglected health care problem and a common complication following breast cancer treatment. Lymphoedema is a well-known predisposing factor for cellulitis, but few have investigated the risk factors for cellulitis in this patient cohort on an international level. The aim of this study was to identify the frequency of cellulitis in patients with lymphoedema of the arm, including potential risk factors for cellulitis. METHODS: An international, multi-centre, cross-sectional study including patients with clinically assessed arm lymphoedema. The primary outcome was the incidence of cellulitis located to the arm with lymphoedema within the last 12 months, and its potential associated risk factors. The secondary outcome was life-time prevalence of cellulitis. Adults with clinically-assessed arm lymphoedema/chronic oedema (all causes) and able to give informed consent were included. End-of-life-patients or those judged as not in the patient's best interest were excluded. Both univariable and multivariable analysis were performed. RESULTS: A total of 2160 patients were included from Australia, Denmark, France, Ireland, Italy, Japan, Turkey and United Kingdom. Secondary lymphoedema was present in 98% of the patients; 95% of these were judged as related to cancer or its treatment. The lifetime prevalence of cellulitis was 22% and 1-year incidence 11%. Following multivariable analysis, factors associated with recent cellulitis were longer swelling duration and having poorly controlled lymphoedema. Compared to having lymphoedema less than 1 year, the risk increased with duration: 1-2 years (OR 2.15), 2-5 years (OR 2.86), 5-10 years (OR 3.15). Patients with well-controlled lymphoedema had a 46% lower risk of cellulitis (OR 0.54, 95% CI 0.39-0.73, p < 0.001). More advanced stages of lymphoedema were associated with cellulitis even after adjustment for swelling duration and control of swelling by logistic regression (stage II OR 5.44, stage III OR 9.13, p = 0.002), demonstrated in a subgroup analysis. CONCLUSION: Patients with advanced arm lymphoedema are at particular risk of developing cellulitis. Prevention of lymphoedema progression is crucial. The results lend towards a positive effect of having well-treated lymphoedema on the frequency of cellulitis.

Toward a Cenozoic history of atmospheric CO2.

The geological record encodes the relationship between climate and atmospheric carbon dioxide (CO2) over long and short timescales, as well as potential drivers of evolutionary transitions. However, reconstructing CO2 beyond direct measurements requires the use of paleoproxies and herein lies the challenge, as proxies differ in their assumptions, degree of understanding, and even reconstructed values. In this study, we critically evaluated, categorized, and integrated available proxies to create a high-fidelity and transparently constructed atmospheric CO2 record spanning the past 66 million years. This newly constructed record provides clearer evidence for higher Earth system sensitivity in the past and for the role of CO2 thresholds in biological and cryosphere evolution.

Self-care treatment for lymphoedema of lymphatic filariasis using integrative medicine.

BACKGROUND: Lymphatic filariasis (LF) is a neglected tropical disease presenting mainly as lymphoedema (elephantiasis). At present, LF is not effectively treated. Integrative medicine (IM) treatment for lymphoedema uses a combination of Indian traditional medicine, Ayurveda, alongside yoga exercises, compression therapy, antibiotics and antifungal treatments, providing a useful combination where resources are limited and different practices are in use. OBJECTIVES: To assess the effectiveness of the IM in the existing clinical practice of lower-limb lymphoedema management and to determine whether the treatment outcomes align with the World Health Organization (WHO) global goal of LF management. METHODS: Institutional data from electronic medical records of all 1698 patients with LF between 2010 and 2019 were retrospectively analysed using pre- and post-treatment comparisons and the National Institute for Health and Care Excellence guidelines for clinical audit. The primary treatment outcomes evaluated were limb volume, bacterial entry points (BEEPs), episodes of cellulitis, and health-related quality of life (HRQoL). Secondary outcomes included the influence of the patient's sex, duration of illness, education and employment status on volume reduction. Multiple regression analysis, t-test, χ2-test, analysis of variance, Mann-Whitney U-test and the Kruskal-Wallis test were used to assess the association between IM and patients' treatment outcomes. RESULTS: Limb volume reduced by 24.5% [95% confidence interval (CI) 22.47-26.61; n = 1660] following an intensive supervised care period (mean 14.84 days, n = 1660). Limb volume further reduced by 1.42% (95% CI 0.76-2.07; n = 1259) at the first follow-up visit (mean 81.45 days), and by 2.3% between the first and second follow-up visits (mean 231.32 days) (95% CI 1.26-3.34; n = 796). BEEPs were reduced upon follow-up; excoriations (78.4%) and intertrigo (26.7%) were reduced at discharge and further improvements was achieved at the follow-up visits. In total, 4% of patients exhibited new BEEPs at the first follow-up [eczema (3.9%), folliculitis (6.5%), excoriations (11.9%) and intertrigo (15.4%); 4 of 7 BEEPs were recorded]. HRQoL, measured using the disease-specific Lymphatic Filariasis Specific Quality of Life Questionnaire, showed an average score of 73.9 on admission, which increased by 17.8 at the first follow-up and 18.6 at the second follow-up. No patients developed new cellulitis episodes at the first follow-up, and only five patients (5.3%) developed new episodes of cellulitis at the second follow-up. CONCLUSIONS: IM for lower-limb lymphoedema successfully reduces limb volume and episodes of cellulitis, and also reduces BEEPs, leading to improved HRQoL. IM aligns with the LF treatment goals of the WHO and is a low-cost, predominantly self-care management protocol. IM has the potential to change care models and improve the lives of patients with lymphoedema.

Dinoflagellate vertical migration fuels an intense red tide.

Harmful algal blooms (HABs) are increasing globally, causing economic, human health, and ecosystem harm. In spite of the frequent occurrence of HABs, the mechanisms responsible for their exceptionally high biomass remain imperfectly understood. A 50-y-old hypothesis posits that some dense blooms derive from dinoflagellate motility: organisms swim upward during the day to photosynthesize and downward at night to access deep nutrients. This allows dinoflagellates to outgrow their nonmotile competitors. We tested this hypothesis with in situ data from an autonomous, ocean-wave-powered vertical profiling system. We showed that the dinoflagellate Lingulodinium polyedra's vertical migration led to depletion of deep nitrate during a 2020 red tide HAB event. Downward migration began at dusk, with the maximum migration depth determined by local nitrate concentrations. Losses of nitrate at depth were balanced by proportional increases in phytoplankton chlorophyll concentrations and suspended particle load, conclusively linking vertical migration to the access and assimilation of deep nitrate in the ocean environment. Vertical migration during the red tide created anomalous biogeochemical conditions compared to 70 y of climatological data, demonstrating the capacity of these events to temporarily reshape the coastal ocean's ecosystem and biogeochemistry. Advances in the understanding of the physiological, behavioral, and metabolic dynamics of HAB-forming organisms from cutting-edge observational techniques will improve our ability to forecast HABs and mitigate their consequences in the future.

A Prospective Preliminary Study Examining the Physiological Impact of Pneumatic Compression Dosing in the Treatment of Lower Extremity Lymphedema.

Background: Optimal frequency and duration of pneumatic compression device (PCD) therapy for lymphedema is undetermined. This prospective, randomized preliminary study evaluated the impact of different PCD dosing protocols on physiological and patient-reported outcomes (PROs) to estimate treatment effects, assess the responsiveness of various measurement techniques, and identify endpoints for a definitive PCD dosing trial. Methods and Results: Twenty-one patients with lower extremity lymphedema were randomized into three groups for treatment with the Flexitouch advanced PCD: (A) once per day for 1 hour, 12 consecutive days; (B) twice per day in 1-hour treatments, 5 consecutive days; or (C) twice per day in 2-hour treatments, 5 consecutive days. Outcomes measured were changes in limb volume (LV), tissue fluid, tissue tone, and PROs. Those in group A experienced mean (standard deviation) LV reductions of 109 (58) mL (p = 0.003) on day 1 and of 97 (86) mL (p = 0.024) on day 5. Group A also showed possible single-treatment decreases in extracellular fluid volume by bioimpedance spectroscopy (BIS) on day 5. There were no consistent changes in groups B and C. Long-term assessment of LV and BIS showed no clear change. Tonometry, ultrasound, local tissue water, and PROs showed wide variation among participants. Conclusions: LV measurements showed potential benefit for 1-hour daily PCD treatment. A definitive dosing trial should include LV, BIS, and PROs in a comparison of 1- and 2-hour daily treatment protocols conducted over a study period of 4 weeks. These data may inform appropriate outcome measures for other intervention studies in lymphedema.

Factors Predicting Limb Volume Reduction Using Compression Bandaging Within Decongestive Lymphatic Therapy in Lymphedema: A Multicountry Prospective Study.

Objectives: To identify predictive factors associated with limb volume reduction using different decongestive lymphatic therapy (DLT) systems in patients with lymphoedema, over a period of up to 28 days. Methods: A multicountry (Canada, France, Germany, the United Kingdom) prospective cohort study using (DLT): skin care, exercise, compression bandaging, and manual lymphatic drainage for up to 4 weeks. Reduction in limb volume comparing DLT with (1) standard multilayer bandaging with inelastic material, and with (2) multilayer bandaging with Coban2, together with the identification of factors associated with limb volume changes. Results: Out of 264 patients with upper or lower limb lymphedema, 133 used Coban2 and 131 used standard care. Following DLT, mean limb volume reduction was 941 mL using Coban2 compared with 814 mL using standard care. A difference of 127 mL was found (95% confidence interval -275 to 529 mL, p = 0.53). Of the 176 patients with leg swelling, 166 (94.3%) had a limb volume measurement after 28 days and were included in the risk factor analysis. Of these, 132 (79.5%) were female, with overall mean age of 60.1 years (standard deviation = 14.7), with secondary lymphedema in 102/163 (62.6%). Duration of lymphedema was >10 years in 75/161 (46.6%) and 99/166 (59.7%) were International Society of Lymphology late-stage II/III, indicating longstanding and/or a high frequency of patients with advanced stages of lymphedema. Ninety-one (54.8%) received Coban2 and 75 (45.2%) had standard care. Multivariable factors for a greater leg volume reduction were large initial leg volume (p < 0.001), DLT treatment duration of 4 weeks compared with 2 weeks (p = 0.01), and peripheral arterial disease (p = 0.015). Conclusion: Limb volume changes were found to be similar between groups. Lack of standardization of DLT makes interpretation of effectiveness problematic. There is an urgent need for randomized-controlled trials. Despite this, severe lymphedema with a large limb volume responded well to DLT in this study.

LIMPRINT in Italy.

Background: To define the profile of patients presenting with chronic edema (CE) in three centers in Italy (Lymphoedema IMpact and PRevalence INTernational). Methods and Results: Data were collected in patients referred for CE between September 2016 and July 2017. A total of 1637 were recruited, 86.7% (1419) outpatients and 13.3% (218) inpatients with 80.6% (1319) female and mean age 54 years. Primary lymphedema occurred in 28.2% (461). In the 71.8% (1176) with secondary CE cancer occurred in 72% (846) and 28% (330) due to other causes. Data showed that 84.2% (226) had full upper body mobility, 15.5% (41) had limited mobility and 0.2% (2) had lost all mobility. Lower limb mobility status: 90.4% (1205) complete mobility, 8.4% (112) reduced mobility and 1.2% (21) wheelchair bound. Concurrent leg ulceration occurred in 32.9% (322) with 3.1% (51) having antibiotics. Treatment patterns varied with only 32.4% (530) receiving instructions in skin care, 61.2% (1002) multilayer compression and a further 67.8% (1110) compression garment with 17.6% (288) having sequential pressure therapy. Only 1.4% (23) had received psychological support. Out of the total 481/1637 (29.4%) were not prescribed any treatment. Only 50.4% (825) had access to subsidized treatments within the National and Regional Health Care System, whereas 49.6% (81) had to pay themselves with only half (50.9%) having access to treatment centers that were near their home. Conclusion: Results from this study and active lobbying have led to changes in reimbursement of care for primary and secondary lymphedema in Italy; this has led to a much more optimistic picture for those affected.

Prevalence and Impact of Chronic Edema in Bariatric Patients: A LIMPRINT Study.

Background: Chronic edema (CO) is a complex condition, arising from different factors, including immobility and obesity. Edema and obesity can have a significant impact on quality of life of patients and their families. Understanding how to manage edema in obese patients is an increasing challenge for both patients and clinicians. As effective treatment options are limited for this population, it is more cost-effective for patients to lose weight before starting treatment. When patients cannot maintain weight loss, one option is to have bariatric surgery. This study was part of LIMPRINT: Lymphedema IMpact and PRevalence INTernational, a study with the aim of identifying the prevalence and impact of CO in different countries and health care settings. Study Purpose: To evaluate the prevalence and impact of CO among patients in a United Kingdom bariatric surgical service. Methods and Results: The gold standard pitting test assessed the presence of edema. General (EuroQOL-5 Dimensions [EQ-5D], RAND 36-Item Short Form Health Survey, Version 1.0 [SF-36], Generalized Anxiety Disorder 7-Item Scale [GAD-7] and Patient Health Questionnaire-9 [PHQ-9]), and edema-specific (Lymphedema Quality of Life [LYMQOL]) quality-of-life questionnaires were used to evaluate impact of edema. The prevalence of edema was 52.1% (25 of 48 participants had edema), potentially linked to obesity, immobility, and medications. Most participants had International Society of Lymphology (ISL) Stage I edema. There were no statistically significant differences between the quality of life of participants with and without edema. However, comparing SF-36 results and normative population data indicated that quality of life was much lower than those in the normative population. Conclusions: This study highlights the high prevalence of edema and low quality of life of this bariatric population. ClinicalTrials.gov ID: NCT03154593.

Association Between Access to Specialists and History of Cellulitis Among Patients with Lymphedema: Secondary Analysis Using the National LIMPRINT Database.

Background: Cellulitis is frequently encountered in patients with lymphedema despite existing prevention protocols. To resolve this issue, social aspects surrounding patients, such as communication with patients and professionals, are necessary to consider new approaches. This study aimed to clarify the association between the history of cellulitis in patients with lymphedema and access to specialists after adjustment for relevant confounding factors. Methods and Results: This study was a secondary analysis of the Lymphoedema IMpact and PRevalence-INTernational (LIMPRINT) study using a national Japanese database of adult lymphedema compiled between 2014 and 2015 (n = 113). Descriptive data were collected for patient characteristics. Multivariate logistic regression analysis was conducted to explore possible risk factors for patients having experienced cellulitis. The duration of edema ranged from <6 months (16.2%) to 10 years or longer (25.2%), with varying severity. History of cellulitis was observed in 31.9% of patients. The prevalent treatment techniques within the context of complex decongestive therapy included skin care advice (52.2%), compression garments (55.8%), exercise advice (41.6%), multilayer bandages (38.1%), cellulitis advice (49.6%), and massage (61.1%). Overall, 57.1% of patients had access to lymphedema specialists. Longer duration of lymphedema (adjusted odds ratio [AOR] = 4.10, p = 0.005) and access to lymphedema specialists (AOR = 0.28, p = 0.009) were significantly associated with a history of cellulitis. Conclusions: A history of cellulitis in patients with lymphedema is associated with limited access to specialists. To support self-care in this patient population, reasonable consideration systems, including telehealth, should be developed to facilitate communication between specialists and patients and decrease the occurrence of cellulitis in lymphedema.

Quality of Life and Costs Within Decongestive Lymphatic Therapy in Patients with Leg Lymphedema: A Multicountry, Open-Label, Prospective Study.

Background: Little is known of the impact in terms of health-related quality of life (HRQoL) and cost-effectiveness with decongestive therapy. Objectives: To examine changes in limb volume, quality of life (QoL), and treatment cost of methods of decongestive lymphatic therapy (DLT). Methods: Patients with chronic edema/lymphedema of the leg were invited to participate in a study of DLT in four countries (United Kingdom, France, Germany, and Canada). In each country two sites were selected. One site used their standard method of DLT in their service, including compression with multilayer bandaging with inelastic material. The other site used a system that included 3M™ Coban 2™ as the bandage treatment alongside other standard components of DLT. Patients were followed for either 2 or 4 weeks depending on the local protocols. At entry, at 2 weeks, and at 4 weeks, patients were assessed by using a health index (EQ-5D), a disease-specific HRQoL tool (LYMQOL) and resource usage was recorded over the treatment period. Results: Of the 165 patients with cost data, 90 were treated with Coban 2 and 75 with standard care compression bandaging. There was good evidence of an improvement in EQ-5D of 0.077 (p < 0.001) in all patients. LYMQOL showed significant improvements (p < 0.001) with lower scores. There were no major differences between the two arms of the study with respect to HRQoL. The number of treatment episodes was higher in those treated with standard care (8.15 vs. 6.37), but the overall treatment cost was higher with Coban 2 (£890.7) compared with standard care (£723.0). Conclusion: QoL improved in the standard care and Coban 2 group bandages, and there was no demonstrable difference between the care systems. Further work is required to examine the role of the individual parts of DLT that provide the greatest benefit to patients and the health systems that support them.

Evolution of rapid blue-light response linked to explosive diversification of ferns in angiosperm forests.

Ferns appear in the fossil record some 200 Myr before angiosperms. However, as angiosperm-dominated forest canopies emerged in the Cretaceous period there was an explosive diversification of modern (leptosporangiate) ferns, which thrived in low, blue-enhanced light beneath angiosperm canopies. A mechanistic explanation for this transformative event in the diversification of ferns has remained elusive. We used physiological assays, transcriptome analysis and evolutionary bioinformatics to investigate a potential connection between the evolution of enhanced stomatal sensitivity to blue light in modern ferns and the rise of angiosperm-dominated forests in the geological record. We demonstrate that members of the largest subclade of leptosporangiate ferns, Polypodiales, have significantly faster stomatal response to blue light than more ancient fern lineages and a representative angiosperm. We link this higher sensitivity to levels of differentially expressed genes in blue-light signaling, particularly in the cryptochrome (CRY) signaling pathway. Moreover, CRYs of the Polypodiales examined show gene duplication events between 212.9-196.9 and 164.4-151.8 Ma, when angiosperms were emerging, which are lacking in other major clades of extant land plants. These findings suggest that evolution of stomatal blue-light sensitivity helped modern ferns exploit the shady habitat beneath angiosperm forest canopies, fueling their Cretaceous hyperdiversification.

Timing is everything: Drivers of interannual variability in blue whale migration.

Blue whales need to time their migration from their breeding grounds to their feeding grounds to avoid missing peak prey abundances, but the cues they use for this are unknown. We examine migration timing (inferred from the local onset and cessation of blue whale calls recorded on seafloor-mounted hydrophones), environmental conditions (e.g., sea surface temperature anomalies and chlorophyll a), and prey (spring krill biomass from annual net tow surveys) during a 10 year period (2008-2017) in waters of the Southern California Region where blue whales feed in the summer. Colder sea surface temperature anomalies the previous season were correlated with greater krill biomass the following year, and earlier arrival by blue whales. Our results demonstrate a plastic response of blue whales to interannual variability and the importance of krill as a driving force behind migration timing. A decadal-scale increase in temperature due to climate change has led to blue whales extending their overall time in Southern California. By the end of our 10-year study, whales were arriving at the feeding grounds more than one month earlier, while their departure date did not change. Conservation strategies will need to account for increased anthropogenic threats resulting from longer times at the feeding grounds.

A view of physical mechanisms for transporting harmful algal blooms to Massachusetts Bay.

Physical dynamics of Harmful Algal Blooms in Massachusetts Bay in May 2005 and 2008 were examined by the simulated results. Reverse particle-tracking experiments suggest that the toxic phytoplankton mainly originated from the Bay of Fundy in 2005 and the western Maine coastal region and its local rivers in 2008. Mechanism studies suggest that the phytoplankton were advected by the Gulf of Maine Coastal Current (GMCC). In 2005, Nor'easters increased the cross-shelf surface elevation gradient over the northwestern shelf. This intensified the Eastern and Western MCC to form a strong along-shelf current from the Bay of Fundy to Massachusetts Bay. In 2008, both Eastern and Western MCC were established with a partial separation around Penobscot Bay before the outbreak of the bloom. The northeastward winds were too weak to cancel or reverse the cross-shelf sea surface gradient, so that the Western MCC carried the algae along the slope into Massachusetts Bay.

A Multinational, Multicenter, Randomized, Double-Blinded, Placebo-Controlled Trial to Evaluate the Efficacy of Cyclical Topical Wound Oxygen (TWO2) Therapy in the Treatment of Chronic Diabetic Foot Ulcers: The TWO2 Study.

OBJECTIVE: Topical oxygen has been used for the treatment of chronic wounds for more than 50 years. Its effectiveness remains disputed due to the limited number of robust high-quality investigations. The aim of this study was to assess the efficacy of multimodality cyclical pressure Topical Wound Oxygen (TWO2) home care therapy in healing refractory diabetic foot ulcers (DFUs) that had failed to heal with standard of care (SOC) alone. RESEARCH DESIGN AND METHODS: Patients with diabetes and chronic DFUs were randomized (double-blind) to either active TWO2 therapy or sham control therapy-both in addition to optimal SOC. The primary outcome was the percentage of ulcers in each group achieving 100% healing at 12 weeks. A group sequential design was used for the study with three predetermined analyses and hard stopping rules once 73, 146, and ultimately 220 patients completed the 12-week treatment phase. RESULTS: At the first analysis point, the active TWO2 arm was found to be superior to the sham arm, with a closure rate of 41.7% compared with 13.5%. This difference in outcome produced an odds ratio (OR) of 4.57 (97.8% CI 1.19, 17.57), P = 0.010. After adjustment for University of Texas Classification (UTC) ulcer grade, the OR increased to 6.00 (97.8% CI 1.44, 24.93), P = 0.004. Cox proportional hazards modeling, also after adjustment for UTC grade, demonstrated >4.5 times the likelihood to heal DFUs over 12 weeks compared with the sham arm with a hazard ratio of 4.66 (97.8% CI 1.36, 15.98), P = 0.004. At 12 months postenrollment, 56% of active arm ulcers were closed compared with 27% of the sham arm ulcers (P = 0.013). CONCLUSIONS: This sham-controlled, double-blind randomized controlled trial demonstrates that, at both 12 weeks and 12 months, adjunctive cyclical pressurized TWO2 therapy was superior in healing chronic DFUs compared with optimal SOC alone.

Prevalence and Risk Factors for Chronic Edema in U.K. Community Nursing Services.

Background and Study Design: Chronic edema (CO) is believed to be a major clinical problem within community nursing services in the United Kingdom. This study was undertaken as part of the LIMPRINT international study to determine the number of people with CO and its impact on health services. Methods and Results: Three urban-based community nursing services participated in the United Kingdom with prospective evaluation for 4 weeks of all patients receiving nursing care using a questionnaire-based interview and clinical assessment using the LIMPRINT tools. Of the total 2541 patients assessed, 1440 (56.7%) were considered to have CO, comprising Leicester City [768/1298 (59.2%)], Nottingham West [124/181 (68.5%)], and Nottingham City [548/1062 (51.6%)]. The mean age for women with CO was 78.6 (standard deviation [SD] 12.8) years and that for men with CO was 72.9 (SD 14.5). More patients with CO suffered from diabetes (32.1% vs. 27.9%, p = 0.027), heart failure/ischemic heart disease (27.3% vs. 14.0%, p < 0.001), and peripheral arterial occlusive disease (5.5% vs. 1.9%, p < 0.001). By far the greatest association was with the presence of a wound (73.6% vs. 37.9%, p < 0.001). Cellulitis affected 628 patients (24.7%) and 688 patients (47.8%) had a concurrent leg ulcer. Rates of reduced mobility (71.6% vs. 61.9%) and obesity were higher in those with CO. Six independent factors associated with CO were service location, age, ethnicity, obesity, heart failure, and the presence of a wound. Conclusion: CO is a major and growing health care problem within primary care that has been previously unrecognized and requires effective service provision.

LIMPRINT: Estimation of the Prevalence of Lymphoedema/Chronic Oedema in Acute Hospital in In-Patients.

Background: To estimate the prevalence of lymphedema/chronic edema (CO) and wounds in acute hospital inpatients in five different countries. Methods and Results: A point-prevalence study was carried out during working day periods in six general hospitals in four countries (Denmark, France, United Kingdom, and Australia) and one hospital oncology inpatient unit in one other country (Ireland). The study used validated clinical tools for the assessment and collection of data. Data were collected by expert clinicians through interviews and physical examination of the patients present in the wards. A total of 1905 patients could be included and investigated among the 3041 total bed occupancy in the seven hospitals. Lymphedema/CO was present in 723 of them (38%). Main risk factors associated with CO were age, morbid obesity, and heart failure, as well as chair bound immobility and neurological deficiency. History of cellulitis was frequent in patients with CO and wounds (24.8%) and CO alone (14.1%) compared to the 1.5% prevalence in patients without CO. Conclusion: Lymphedema/CO is very frequent in patients hospitalized in hospital acute wards. It is strongly associated with obesity, venous insufficiency, and heart failure. Our results strongly suggest a hidden health care burden and cost linked to CO independently of chronic wounds.

LIMPRINT: Prevalence of Chronic Edema in Health Services in Copenhagen, Denmark.

Background: The International Lymphedema Framework developed an international study, Lymphedema Impact and Prevalence International (LIMPRINT), to estimate the prevalence and impact of chronic edema (CO) in heterogeneous populations. Methods and Results: A validation study using the LIMPRINT methodology was undertaken in Denmark. Participants with CO were identified from inpatient services and compared with those identified within a specialist lymphedema service and three primary care settings. Of 452 inpatients available for screening, CO was present in 177 (39%) and absent in 275 (61%). In addition, 723 participants were found from specialist and primary care services (LPCSs). Inpatients were significantly older and more likely to be underweight or normal weight. They were more likely to suffer from heart failure/ischaemic heart disease (44.6% vs. 23.4%, p < 0.001) and have neurological problems (18.1% vs. 10.9% p = 0.009). Patients in the inpatient group were nearly all suffering from secondary lymphedema and were less likely to have a cancer or venous diagnosis, but more likely to have immobility as the cause of CO (44.0% vs. 17.7%, p < 0.001). No inpatients had midline CO compared with 30 within LPCSs. Fewer in the inpatient group had standard CO treatment (17.1% vs. 73.5%, p < 0.001) and subjective control of swelling was worse (19.9% vs. 66.7%, p < 0.001). While the inpatient group experienced fewer acute infections, when they did so, they were more likely to be admitted to hospital for this (78.6% vs. 51.0%, p = 0.049). Conclusion: The prevalence of CO in inpatient facilities is high and those with CO have multiple comorbidities that vary according to setting. The feasibility study showed that the methodology could be adapted for use in different health systems.

LIMPRINT: The UK Experience-Subjective Control of Swelling in Patients Attending Specialist Lymphedema Services.

Background and Study Design: This study was undertaken as part of the UK LIMPRINT international study to determine the number of people with chronic edema (CO) and its impact on health services. Overall 7436 with CO were recruited in the main UK study from a range of health settings. Methods and Results: Factors relating to subjective control of arm and leg CO were defined in the UK. A total of 1565 patients were included in the study with exclusions for: no limb swelling or not recorded (1669), having concurrent arm/leg CO (272), control of assessment missing (5) and professional being unsure of control status of CO (325). Arm swelling occurred in 953 (18.5%) with leg CO in 4212 (81.5%). Poor control was found in 1430 (27.2%) and good control in 3735 (72.3%). Control of arm swelling was worse in men and control increased overall in those aged over 45 years. In contrast control of CO worsened in those with leg CO with increasing age and multiple co-morbidities. Obesity and cellulitis, particularly an episode in the last year were associated with poor control. Independent risk factors for arm CO were : obesity, neurological disease and cellulitis in the last year and for leg CO, obesity, poor mobility, heart disease, presence of a wound, cellulitis in the last year and duration of swelling. Conclusion: Control of CO within specialized centers is complex due to sociodemographic and clinical comorbidities.

Evolution of chloroplast retrograde signaling facilitates green plant adaptation to land.

Chloroplast retrograde signaling networks are vital for chloroplast biogenesis, operation, and signaling, including excess light and drought stress signaling. To date, retrograde signaling has been considered in the context of land plant adaptation, but not regarding the origin and evolution of signaling cascades linking chloroplast function to stomatal regulation. We show that key elements of the chloroplast retrograde signaling process, the nucleotide phosphatase (SAL1) and 3'-phosphoadenosine-5'-phosphate (PAP) metabolism, evolved in streptophyte algae-the algal ancestors of land plants. We discover an early evolution of SAL1-PAP chloroplast retrograde signaling in stomatal regulation based on conserved gene and protein structure, function, and enzyme activity and transit peptides of SAL1s in species including flowering plants, the fern Ceratopteris richardii, and the moss Physcomitrella patens Moreover, we demonstrate that PAP regulates stomatal closure via secondary messengers and ion transport in guard cells of these diverse lineages. The origin of stomata facilitated gas exchange in the earliest land plants. Our findings suggest that the conquest of land by plants was enabled by rapid response to drought stress through the deployment of an ancestral SAL1-PAP signaling pathway, intersecting with the core abscisic acid signaling in stomatal guard cells.