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Background Worldwide, up to 20 % of hospitalised patients have diabetes mellitus. In-hospital dysglycaemia increases patient mortality, morbidity, and length of hospital stay. Improved in-hospital diabetes management strategies are needed. The DIATEC trial investigates the effects of an in-hospital diabetes team and operational insulin titration algorithms based on either continuous glucose monitoring (CGM) data or standard point-of-care (POC) glucose testing. Methods This is a two-armed, two-site, prospective randomised open-label blinded endpoint (PROBE) trial. We recruit non-critically ill hospitalised general medical and orthopaedic patients with type 2 diabetes treated with basal, prandial, and correctional insulin (N = 166). In both arms, patients are monitored by POC glucose testing and diabetes management is done by ward nurses guided by in-hospital diabetes teams. In one of the arms, patients are monitored in addition to POC glucose testing by telemetric CGM viewed by the in-hospital diabetes teams only. The in-hospital diabetes teams have operational algorithms to titrate insulin in both arms. Outcomes are in-hospital glycaemic and clinical outcomes. Discussion The DIATEC trial will show the glycaemic and clinical effects of in-hospital CGM handled by in-hospital diabetes teams with access to operational insulin titration algorithms in non-critically ill patients with type 2 diabetes. The DIATEC trial seeks to identify which hospitalised patients will benefit from CGM and in-hospital diabetes teams compared to POC glucose testing. This is essential information to optimise the use of healthcare resources before broadly implementing in-hospital CGM and diabetes teams., Background: Worldwide, up to 20 % of hospitalised patients have diabetes mellitus. In-hospital dysglycaemia increases patient mortality, morbidity, and length of hospital stay. Improved in-hospital diabetes management strategies are needed. The DIATEC trial investigates the effects of an in-hospital diabetes team and operational insulin titration algorithms based on either continuous glucose monitoring (CGM) data or standard point-of-care (POC) glucose testing. Methods: This is a two-armed, two-site, prospective randomised open-label blinded endpoint (PROBE) trial. We recruit non-critically ill hospitalised general medical and orthopaedic patients with type 2 diabetes treated with basal, prandial, and correctional insulin (N = 166). In both arms, patients are monitored by POC glucose testing and diabetes management is done by ward nurses guided by in-hospital diabetes teams. In one of the arms, patients are monitored in addition to POC glucose testing by telemetric CGM viewed by the in-hospital diabetes teams only. The in-hospital diabetes teams have operational algorithms to titrate insulin in both arms. Outcomes are in-hospital glycaemic and clinical outcomes. Discussion: The DIATEC trial will show the glycaemic and clinical effects of in-hospital CGM handled by in-hospital diabetes teams with access to operational insulin titration algorithms in non-critically ill patients with type 2 diabetes. The DIATEC trial seeks to identify which hospitalised patients will benefit from CGM and in-hospital diabetes teams compared to POC glucose testing. This is essential information to optimise the use of healthcare resources before broadly implementing in-hospital CGM and diabetes teams. Trial registration: Prospectively registered at ClinicalTrials.gov with identification number NCT05803473 on March 27th 2023.

The diverse range of organizations contributing to the global research ecosystem is believed to enhance the overall quality and resilience of its output. Mid-sized autonomous research institutes, distinct from universities, play a crucial role in this landscape. They often lead the way in new research fields and experimental methods, including those in social and organizational domains, which are vital for driving innovation. The EU-LIFE alliance was established with the goal of fostering excellence by developing and disseminating best practices among European biomedical research institutes. As directors of the 15 EU-LIFE institutes, we have spent a decade comparing and refining our processes. Now, we are eager to share the insights we've gained. To this end, we have crafted this Charter, outlining 10 principles we deem essential for research institutes to flourish and achieve ground-breaking discoveries. These principles, detailed in the Charter, encompass excellence, independence, training, internationality and inclusivity, mission focus, technological advancement, administrative innovation, cooperation, societal impact, and public engagement. Our aim is to inspire the establishment of new institutes that adhere to these principles and to raise awareness about their significance. We are convinced that they should be viewed a crucial component of any national and international innovation strategies.

Purpose To investigate the role of E. coli virulence-associated genes (VAGs) in predicting urinary tract infection (UTI) as the source of bacteremia in two distinct hospital populations, one with a large general catchment area and one dominated by referrals. Methods E. coli bacteremias identified at Department of Clinical Microbiology (DCM), Hvidovre Hospital and DCM, Rigshospitalet in the Capital Region of Denmark from October to December 2018. Using whole genome sequencing (WGS), we identified 358 VAGs from 224 E. coli bacteremia. For predictive analysis, VAGs were paired with clinical source of UTI from local bacteremia databases. Results VAGs strongly predicting of UTI as primary infection source of bacteremia were primarily found within the pap gene family. papX (PPV 96%, sensitivity 54%) and papGII (PPV 93%, sensitivity 56%) were found highly predictive, but showed low sensitivities. The strength of VAG predictions of UTI as source varied significantly between the two hospital populations. VAGs had weaker predictions in the tertiary referral center (Rigshospitalet), a disparity likely stemming from differences in patient population and department specialization. Conclusion WGS data was used to predict the primary source of E. coli bacteremia and is an attempt on a new and different type of infection source identification. Genomic data showed potential to be utilized to predict the primary source of infection; however, discrepancy between the best performing profile of VAGs between acute care hospitals and tertiary hospitals makes it difficult to implement in clinical practice., Purpose: To investigate the role of E. coli virulence-associated genes (VAGs) in predicting urinary tract infection (UTI) as the source of bacteremia in two distinct hospital populations, one with a large general catchment area and one dominated by referrals. Methods: E. coli bacteremias identified at Department of Clinical Microbiology (DCM), Hvidovre Hospital and DCM, Rigshospitalet in the Capital Region of Denmark from October to December 2018. Using whole genome sequencing (WGS), we identified 358 VAGs from 224 E. coli bacteremia. For predictive analysis, VAGs were paired with clinical source of UTI from local bacteremia databases. Results: VAGs strongly predicting of UTI as primary infection source of bacteremia were primarily found within the pap gene family. papX (PPV 96%, sensitivity 54%) and papGII (PPV 93%, sensitivity 56%) were found highly predictive, but showed low sensitivities. The strength of VAG predictions of UTI as source varied significantly between the two hospital populations. VAGs had weaker predictions in the tertiary referral center (Rigshospitalet), a disparity likely stemming from differences in patient population and department specialization. Conclusion: WGS data was used to predict the primary source of E. coli bacteremia and is an attempt on a new and different type of infection source identification. Genomic data showed potential to be utilized to predict the primary source of infection; however, discrepancy between the best performing profile of VAGs between acute care hospitals and tertiary hospitals makes it difficult to implement in clinical practice.

OBJECTIVES: Preclinically, curcumin has been shown to protect against glucocorticoid-induced insulin resistance. We evaluated the effect of curcumin administered with prednisolone in healthy overweight or obese men.METHODS: In a double-blind, parallel-group trial, 24 overweight/obese non-diabetic men were randomised to one of three intervention groups A) prednisolone placebo+curcumin placebo, B) prednisolone (50 mg/day)+curcumin placebo or C) prednisolone and curcumin (400 mg/day). Curcumin or curcumin placebo treatment started one day prior to 10-day prednisolone or prednisolone placebo treatment. The primary endpoint was change in prednisolone-induced insulin resistance assessed by homeostatic model assessment of insulin resistance (HOMA2-IR). Other endpoints included anthropometric measurements, magnetic resonance spectroscopy-assessed hepatic fat content, blood pressure, circulating metabolic markers and continuous glucose monitoring measures.RESULTS: Baseline characteristics (mean ± SD): age 44.2 ± 13.7 years, body mass index 30.1 ± 3.5 kg/m2, glycated haemoglobin A1c 33.3 ± 3.2 mmol/mol, HOMA2-IR 1.10 ± 0.45 and fasting plasma glucose 5.2 ± 0.4 mmol/L. Prednisolone significantly increased HOMA2-IR (estimated treatment difference 0.36 [95% CI 0.16; 0.57]). Co-treatment with curcumin had no effect on HOMA2-IR (estimated treatment difference 0.08 [95% CI -0.13; 0.39]). Prednisolone increased glycated haemoglobin A1c, insulin, C-peptide, glucagon, blood pressure, mean interstitial glucose, time spent in hyperglycaemia and glucose variability, but no protective effect of curcumin on any of these measures was observed.CONCLUSIONS: In this double-blind, placebo-controlled parallel-group study involving 24 overweight or obese men randomised to one of three treatment arms, curcumin treatment had no protective effect on prednisolone-induced insulin resistance or other gluco-metabolic perturbations.

Background: Childhood trauma (CT) are frequently reported by patients with bipolar disorder (BD), but it is unclear whether and how CT contribute to patients’ cognitive and psychosocial impairments. We aimed to examine the impact of CT on cognition and psychosocial functioning in a large sample of 345 patients with BD and 183 healthy control participants (HC) using the Childhood Trauma Questionnaire, neurocognitive tests and ratings of mood symptoms and functioning. Results: Patients showed broad cognitive impairments across memory, attention and executive function and functional disability despite being in partial or full remission and had higher levels of CT than HC. Higher levels of CT correlated with impairments across almost all cognitive domains and lower psychosocial functioning across BD patients and HC. Of these, the associations between CT and poorer working memory and lower psychosocial functioning, respectively, prevailed after adjusting for clinical and demographical variables. Diagnosis of BD and estimated verbal intelligence did not moderate these associations. Analysis of CT sub-categories showed that working memory impairments were related particularly to childhood physical and emotional abuse, while psychosocial difficulties were related to physical and emotional neglect. Conclusions: CT may have negative implications for working memory and psychosocial functioning across both BD and healthy populations. If the findings are replicated, this would suggest that early interventions that reduce the frequency of CT in vulnerable families may aid children’s cognitive and psychosocial development.

INTRODUCTION. Insulin is the preferred treatment for hyperglycaemia in hospitalised patients with type 2 diabetes mellitus (T2DM). However, which insulin regimen to prefer is debated. We described Danish regional guidelines on the management of non-critically ill hospitalised patients with T2DM and compared them with international guidelines. METHODS. The Danish regional guidelines have been obtained via Danish regional web portals and by request to the regions. The guidelines were reviewed independently by the authors of this article to ensure uniformity in the interpretation of their contents. RESULTS. The recommended treatment of in-hospital hyperglycaemia is sliding scale insulin (SSI) in all five Danish regions. Insulin dosing by SSI is adjusted to bodyweight in two of the five regions. The recommended number of daily glucose point-of- care tests ranges from 4-8 to reach glucose levels of 5-10 mmol/l (90-180 mg/dl). In all regions, continuation of out-hospital insulin and non-insulin antidiabetic drugs is recommended; however, the latter is paused on wide indications. CONCLUSIONS. In-hospital hyperglycaemia for non-critically ill hospitalised patients with T2DM is treated by SSI, based on short-acting insulin, in all five Danish regions. International guidelines recommend a basal-bolus or basal-plus regimen based on both short- and long-acting insulin for most hospitalised non-critically ill patients with diabetes and discourage SSI. Danish regions should consider replacing SSI with a basal-bolus or basal-plus regimen. FUNDING. none. TRIAL REGISTRATION. not relevant., INTRODUCTION. Insulin is the preferred treatment for hyperglycaemia in hospitalised patients with type 2 diabetes mellitus (T2DM). However, which insulin regimen to prefer is debated. We described Danish regional guidelines on the management of non-critically ill hospitalised patients with T2DM and compared them with international guidelines. METHODS. The Danish regional guidelines have been obtained via Danish regional web portals and by request to the regions. The guidelines were reviewed independently by the authors of this article to ensure uniformity in the interpretation of their contents. RESULTS. The recommended treatment of in-hospital hyperglycaemia is sliding scale insulin (SSI) in all five Danish regions. Insulin dosing by SSI is adjusted to bodyweight in two of the five regions. The recommended number of daily glucose point-of-care tests ranges from 4-8 to reach glucose levels of 5-10 mmol/l (90-180 mg/dl). In all regions, continuation of out-hospital insulin and non-insulin antidiabetic drugs is recommended; however, the latter is paused on wide indications. CONCLUSIONS. In-hospital hyperglycaemia for non-critically ill hospitalised patients with T2DM is treated by SSI, based on short-acting insulin, in all five Danish regions. International guidelines recommend a basal-bolus or basal-plus regimen based on both short-and long-acting insulin for most hospitalised non-critically ill patients with diabetes and discourage SSI. Danish regions should consider replacing SSI with a basal-bolus or basal-plus regimen.

Aims The aim of our meta-analyses was to compare the effects of glucose-lowering drugs on mortality, cardiovascular and renal endpoints for a range of type 2 diabetes (T2D) subgroups defined by their specific cardiovascular risk profile. Methods Meta-analyses comparing drugs within the classes of GLP-1RAs and SGLT-2 inhibitors were performed and compared to sulphonylureas and DPP-4 inhibitors with available cardiovascular outcome trials. The comparison between the different classes of glucose-lowering drugs included analyses of T2D populations with low risk and high risk for cardiovascular disease including populations with established cardiovascular disease and/or kidney disease. Outcomes included mortality, major cardiovascular adverse events (MACE), hospitalisation for heart failure (HHF) and a composite renal endpoint as applied in the underlying clinical trials. Results SGLT-2 inhibitors and GLP-1RAs showed beneficial effects on mortality and MACE compared to the classes of DPP-4 inhibitors and sulphonylureas. SGLT-2 inhibitors were shown to be the most effective treatment in terms of HHF and kidney disease. Metformin was used as background therapy for the vast majority of participants in all included studies. Overall, the absolute effects of SGLT-2 inhibitors and GLP-1RAs on these important outcomes were evident for patients with established or at high risk for cardiovascular disease but limited for the low-risk subgroup. Conclusions The findings from our analyses substantiate the relevance of treatment with SGLT-2 inhibitors or GLP-1RAs as an add-on to metformin in patients with T2D and a high risk for cardiovascular disease, and furthermore, support the recommendation for SGLT-2 inhibitor treatment in patients with T2D and heart failure or established kidney disease., Aims: The aim of our meta-analyses was to compare the effects of glucose-lowering drugs on mortality, cardiovascular and renal endpoints for a range of type 2 diabetes (T2D) subgroups defined by their specific cardiovascular risk profile. Methods: Meta-analyses comparing drugs within the classes of GLP-1RAs and SGLT-2 inhibitors were performed and compared to sulphonylureas and DPP-4 inhibitors with available cardiovascular outcome trials. The comparison between the different classes of glucose-lowering drugs included analyses of T2D populations with low risk and high risk for cardiovascular disease including populations with established cardiovascular disease and/or kidney disease. Outcomes included mortality, major cardiovascular adverse events (MACE), hospitalisation for heart failure (HHF) and a composite renal endpoint as applied in the underlying clinical trials. Results: SGLT-2 inhibitors and GLP-1RAs showed beneficial effects on mortality and MACE compared to the classes of DPP-4 inhibitors and sulphonylureas. SGLT-2 inhibitors were shown to be the most effective treatment in terms of HHF and kidney disease. Metformin was used as background therapy for the vast majority of participants in all included studies. Overall, the absolute effects of SGLT-2 inhibitors and GLP-1RAs on these important outcomes were evident for patients with established or at high risk for cardiovascular disease but limited for the low-risk subgroup. Conclusions: The findings from our analyses substantiate the relevance of treatment with SGLT-2 inhibitors or GLP-1RAs as an add-on to metformin in patients with T2D and a high risk for cardiovascular disease, and furthermore, support the recommendation for SGLT-2 inhibitor treatment in patients with T2D and heart failure or established kidney disease.

I Danmark formodes 10-15% af indlagte patienter at have diabetes [1]. Adskillige faktorer påvirker glukosemetabolismen under indlæggelse. Øget insulinbehov ses bl.a. ved opblussen i kronisk sygdom, infektioner og feber, immobilisering, glukokortikoidbehandling og kirurgi. Faste sænker derimod insulinbehovet, mens nyre- og leverpåvirkning ændrer omsætningen af oralt givet antidiabetika og GLP-1-receptoragonister. I et travlt og subspecialiseret sundhedsvæsen kan håndteringen af disse hurtigt omskiftelige faktorer være udfordrende. Dette kan resultere i dysglykæmi, dvs. hypoglykæmi, hyperglykæmi og blodsukkerudsving, kaldet glykæmisk variabilitet. Dysglykæmien er forbundet med øget indlæggelsestid, øget mortalitet og komplikationer under hospitalsindlæggelse, Diabetes and hyperglycaemia are frequent diagnoses in the hospital, and in-hospital hyperglycaemia isassociated with adverse clinical outcomes. Insulin is the preferred treatment for in-hospital hyperglycaemia. This review summarises the management of hyperglycaemia in Danish hospitals. In Denmark, sliding-scaleinsulin is often applied with the addition of basal insulin after 1-2 days with hyperglycaemia which differs frominternational guidelines recommending a basal-bolus regimen. The optimal non-intensive care unit glucosetargets, the safety and efficacy level of non-insulin antidiabetic agents, and continuous glucose monitoring aresubjects of further research.

Process-based, mechanistic research of mineral authigenesis has been progressively utilized to understand the biogeochemical processes taking place at the sediment¿water interface (SWI), and to capture long-term sedimentary (biogeochemical) records of paleoenvironments. A better understanding of mineral authigenic sedimentary processes directly beneath the SWI in Arctic continental shelves is thus fundamental as Earth¿s polar regions are at greatest risk of future climate change. This is in part due to disturbances in the benthic¿pelagic coupling related to changes in ocean circulation and sea ice dynamics. In this study, we aim at focusing on the Holocene period by investigating sedimentary archives recovered from the NE Greenland shelf during the NorthGreen17 Expedition. Here we combined a suite of sedimentological (e.g., detailed ichnological analysis and taphonomic features of the benthic foraminifera Cassidulina neoteretis), mineralogical (bulk and clay mineralogy) and geochemical (major, trace and rare earth elements, and ¿13C and ¿18O stable isotope signatures recorded in Cassidulina neoteretis) proxies with bulk organic matter parameters (¿13C, TOC, TN). The first results of this study, presented during the EGU General Assembly 2023 in Vienna, Austria, focus on several important points such as: (1) changes in sedimentation (geochemical characteristics) over the NE Greenland sediment profiles; (2) evolutionary characteristics of terrigenous influx, redox conditions and productivity; and (3) controlling factors and modes of organic matter accumulation.

Diabetes and hyperglycaemia are frequent diagnoses in the hospital, and in-hospital hyperglycaemia is associated with adverse clinical outcomes. Insulin is the preferred treatment for in-hospital hyperglycaemia. This review summarises the management of hyperglycaemia in Danish hospitals. In Denmark, sliding-scale insulin is often applied with the addition of basal insulin after 1-2 days with hyperglycaemia which differs from international guidelines recommending a basal-bolus regimen. The optimal non-intensive care unit glucose targets, the safety and efficacy level of non-insulin antidiabetic agents, and continuous glucose monitoring are subjects of further research.

Perceived physical exertion is increased when exercise is performed on metformin treatment, but the clinical relevance of this is unknown. In this post hoc analysis of a randomized, controlled trial, we investigated whether metformin treatment was associated with lower levels of free-living physical activity. Ninety individuals with overweight/obesity (BMI>25 m2/kg) and HbA1c-defined prediabetes (39-47 mmol/mol) were randomized to treatment with dapagliflozin (SGLT2-inhibitor; 10 mg once daily, n=30), metformin (850 mg twice daily, n=30) or no treatment (control, n=30) for 13 weeks in a parallel-group, open-label trial. Before (baseline), during (6 weeks) and immediately after (13 weeks) cessation of treatment, a 6-day assessment of physical activity and sedentary behaviour was performed using accelerometer-based physical activity monitors. Intention-to-treat analyses revealed no within-group changes or differences in change between the groups for any measures of physical activity or sedentary behaviour at neither 6 nor 13 weeks. Short-term metformin treatment does not reduce free-living physical activity level in individuals with overweight/obesity and HbA1c-defined prediabetes., Perceived physical exertion is increased when exercise is performed on metformin treatment, but the clinical relevance of this is unknown. In this post hoc analysis of a randomized, controlled trial, we investigated whether metformin treatment was associated with lower levels of free-living physical activity. Ninety individuals with overweight/obesity (BMI>25 m2/kg) and HbA1c-defined prediabetes (39-47 mmol/mol) were randomized to treatment with dapagliflozin (SGLT2-inhibitor; 10 mg once daily, n=30), metformin (850 mg twice daily, n=30) or no treatment (control, n=30) for 13 weeks in a parallel-group, open-label trial. Before (baseline), during (6 weeks) and immediately after (13 weeks) cessation of treatment, a 6-day assessment of physical activity and sedentary behaviour was performed using accelerometer-based physical activity monitors. Intention-to-treat analyses revealed no within-group changes or differences in change between the groups for any measures of physical activity or sedentary behaviour at neither 6 nor 13 weeks. Short-term metformin treatment does not reduce free-living physical activity level in individuals with overweight/obesity and HbA1c-defined prediabetes.

International Humanitarian Law (IHL) aims to limit the effects of armed conflict. It divides the world into legitimate military objectives that may be lawfully targeted during armed conflict, and protected civil ian persons and objects that are to be protected from attack. IHL provides clear guidance on how to distinguish one category from the other – at least in the physical realm. The relatively new domain of cyberspace, however, is characterized by a number of features unknown at the time of IHL’s foundation. As a consequence, there is currently no consensus on whether and how the rules on targeting apply to digital data. However, recent examples from the war in Ukraine have shown that cyberspace and attacks on data are part of modern armed conflicts, and the question of the legal status of data in IHL is therefore highly topical. On that basis, this report investigates whether data should be understood as protected civilian objects through an analysis of the legal debate on the matter and statements made by states in this regard. The report identifies two major positions in the legal debate on the status of data: The traditionalist school, which emphasizes the fact that ‘an object’ has traditionally been defined as something visible and tangible, and that data therefore should not be considered an object, as the protection provided by IHL would otherwise extend beyond its intended scope; and the progressive school, which emphasizes that the purpose of IHL is to protect civilians from the effects of armed conflict, and that civilian data should therefore be considered an object, as the protections provided by IHL would otherwise be more restricted than intended. Both schools posit valid legal interpretations but arrive at polar opposite conclusions. This report therefore suggests a contextual interpretation as a supplement to the two schools: As the rules and legal structure of relevant IHL regulation intend to divide the world into objects that are either legiti

A key contemporary challenge for international lawyers is to determine how international humanitarian law (ihl) applies to cyber operations. This involves determining how ihl language – devised for the physical world – can be translated into usable concepts for the digital age. Often, this is done largely by balancing the ‘ordinary meaning’ of specific ihl concepts against the ‘object and purpose’ of ihl treaties. This, at least, has been the case in the debate on whether the concept of ‘objects’ include or exclude (digital) data. Contributors to this debate often emphasise this balancing act, but also seem guided by what they consider acceptable outcomes. Specifically, they argue that what is legal in the analogue, physical world should not be rendered illegal through digitisation and vice versa. This article argues that this approach is unhelpful as it leads to conflicting results. Instead, we argue that the addition of a contextual analysis could help move the debate forward.

Seventy five percent of the world's food crops benefit from insect pollination. Hence, there has been increased interest in how global change drivers impact this critical ecosystem service. Because standardized data on crop pollination are rarely available, we are limited in our capacity to understand the variation in pollination benefits to crop yield, as well as to anticipate changes in this service, develop predictions, and inform management actions. Here, we present CropPol, a dynamic, open and global database on crop pollination. It contains measurements recorded from 202 crop studies, covering 3,394 field observations, 2,552 yield measurements (i.e. berry weight, number of fruits and kg per hectare, among others), and 47,752 insect records from 48 commercial crops distributed around the globe. CropPol comprises 32 of the 87 leading global crops and commodities that are pollinator dependent. Malus domestica is the most represented crop (32 studies), followed by Brassica napus (22 studies), Vaccinium corymbosum (13 studies), and Citrullus lanatus (12 studies). The most abundant pollinator guilds recorded are honey bees (34.22% counts), bumblebees (19.19%), flies other than Syrphidae and Bombyliidae (13.18%), other wild bees (13.13%), beetles (10.97%), Syrphidae (4.87%), and Bombyliidae (0.05%). Locations comprise 34 countries distributed among Europe (76 studies), Northern America (60), Latin America and the Caribbean (29), Asia (20), Oceania (10), and Africa (7). Sampling spans three decades and is concentrated on 2001-05 (21 studies), 2006-10 (40), 2011-15 (88), and 2016-20 (50). This is the most comprehensive open global data set on measurements of crop flower visitors, crop pollinators and pollination to date, and we encourage researchers to add more datasets to this database in the future. This data set is released for non-commercial use only. Credits should be given to this paper (i.e., proper citation), and the products generated with this database should

As the world becomes increasingly urban, cities are seeking creative and effective strategies to become more climate-proof and sustainable while, at the same time, creating liveable urban futures. Although it is often positioned as such an all-encompassing solution, urban greening has been found to give rise to new injustices and produce paradoxical effects of green gentrification. In combining documentary materials and interviews with city planners, this thesis explores questions of inclusion and equity in urban greening initiatives in Lund, Sweden. It is found that while steps are taken to include residents in the process and ensure equitable outcomes, there are shortcomings and constraints regarding how to generate valuable insight from citizen participation as well as navigating the array of preferences and objectives associated with urban planning. In the end, these can have important implications for residents’ sense of control and the ability to establish socially sound urban greening.

Seventy five percent of the world's food crops benefit from insect pollination. Hence, there has been increased interest in how global change drivers impact this critical ecosystem service. Because standardized data on crop pollination are rarely available, we are limited in our capacity to understand the variation in pollination benefits to crop yield, as well as to anticipate changes in this service, develop predictions, and inform management actions. Here, we present CropPol, a dynamic, open, and global database on crop pollination. It contains measurements recorded from 202 crop studies, covering 3,394 field observations, 2,552 yield measurements (i.e., berry mass, number of fruits, and fruit density [kg/ha], among others), and 47,752 insect records from 48 commercial crops distributed around the globe. CropPol comprises 32 of the 87 leading global crops and commodities that are pollinator dependent. Malus domestica is the most represented crop (32 studies), followed by Brassica napus (22 studies), Vaccinium corymbosum (13 studies), and Citrullus lanatus (12 studies). The most abundant pollinator guilds recorded are honey bees (34.22% counts), bumblebees (19.19%), flies other than Syrphidae and Bombyliidae (13.18%), other wild bees (13.13%), beetles (10.97%), Syrphidae (4.87%), and Bombyliidae (0.05%). Locations comprise 34 countries distributed among Europe (76 studies), North America (60), Latin America and the Caribbean (29), Asia (20), Oceania (10), and Africa (7). Sampling spans three decades and is concentrated on 2001–2005 (21 studies), 2006–2010 (40), 2011–2015 (88), and 2016–2020 (50). This is the most comprehensive open global data set on measurements of crop flower visitors, crop pollinators and pollination to date, and we encourage researchers to add more datasets to this database in the future. This data set is released for non-commercial use only. Credits should be given to this paper (i.e., proper citation), and the products generated with this da

The western Fram Strait is the only deep-water gateway connecting the Arctic Ocean and North Atlantic. Consequently, today, the western Fram Strait and the Northeast Greenland shelf receive cold, low saline Polar and Arctic Atlantic waters from the Arctic Ocean incorporated in the East Greenland Current, together with warmer, saline recirculated Atlantic Water masses derived from the West Spitsbergen Current. We present a multiproxy study (grain size distribution, XRF core scans, and benthic foraminiferal assemblages) based on the lower part of the radiocarbon dated marine sediment core DA17-NG-ST03-039G, covering the period from 13.3 to 3.9 cal ka BP. We reconstruct the deglacial conditions of the Northeast Greenland shelf together with Early to Mid Holocene fluctuations in subsurface Atlantic Water and Polar Water advection. The results show that the outer Northeast Greenland shelf was deglaciated and marine conditions were established prior to c. 13.3 cal ka BP. At this time, our data show Atlantic Water masses flowing beneath an extensive sea-ice cover in a glaciomarine setting, potentially related to the Bølling-Allerød warm period. Around 12.9 cal ka BP, the onset of high surface and bottom water productivity may be associated with the Younger Dryas onset. This was followed by a transition towards warmer bottom and subsurface water conditions from c. 11.7 until 10.2 cal ka BP caused by enhanced advection of Atlantic-derived water masses. A cold period with marginal ice zone conditions and enhanced East Greenland Current incursion is evident from 10.2 to 9.4 cal ka BP, succeeded by harsher sea-ice conditions and Atlantic Water inflow, prevailing until c. 7.5 cal ka BP. Holocene Thermal Maximum conditions, characterized by high surface and subsurface water productivity, were promoted by enhanced Atlantic Water flow to the shelf from c. 7.5 to 6.7 cal ka BP. In contrast, the transition towards a cold period with increased drift-ice transport via a strong East Gre

Seventy five percent of the world's food crops benefit from insect pollination. Hence, there has been increased interest in how global change drivers impact this critical ecosystem service. Because standardized data on crop pollination are rarely available, we are limited in our capacity to understand the variation in pollination benefits to crop yield, as well as to anticipate changes in this service, develop predictions, and inform management actions. Here, we present CropPol, a dynamic, open, and global database on crop pollination. It contains measurements recorded from 202 crop studies, covering 3,394 field observations, 2,552 yield measurements (i.e., berry mass, number of fruits, and fruit density [kg/ha], among others), and 47,752 insect records from 48 commercial crops distributed around the globe. CropPol comprises 32 of the 87 leading global crops and commodities that are pollinator dependent. Malus domestica is the most represented crop (32 studies), followed by Brassica napus (22 studies), Vaccinium corymbosum (13 studies), and Citrullus lanatus (12 studies). The most abundant pollinator guilds recorded are honey bees (34.22% counts), bumblebees (19.19%), flies other than Syrphidae and Bombyliidae (13.18%), other wild bees (13.13%), beetles (10.97%), Syrphidae (4.87%), and Bombyliidae (0.05%). Locations comprise 34 countries distributed among Europe (76 studies), North America (60), Latin America and the Caribbean (29), Asia (20), Oceania (10), and Africa (7). Sampling spans three decades and is concentrated on 2001¿2005 (21 studies), 2006¿2010 (40), 2011¿2015 (88), and 2016¿2020 (50). This is the most comprehensive open global data set on measurements of crop flower visitors, crop pollinators and pollination to date, and we encourage researchers to add more datasets to this database in the future.

Aims/hypothesis: This secondary analysis aimed to investigate the effects of a 12 months intensive exercise-based lifestyle intervention on systemic markers of oxidative stress in persons with type 2 diabetes. We hypothesized lifestyle intervention to be superior to standard care in decreasing levels of oxidative stress. Methods: The study was based on the single-centre, assessor-blinded, randomised, controlled U-turn trial (ClinicalTrial.gov NCT02417012). Persons with type 2 diabetes ˂ 10 years, ˂ 3 glucose lowering medications, no use of insulin, BMI 25–40 kg/m2 and no severe diabetic complications were included. Participants were randomised (2:1) to either intensive exercise-based lifestyle intervention and standard (n = 64) or standard care alone (n = 34). Standard care included individual education in diabetes management, advice on a healthy lifestyle and regulation of medication by a blinded endocrinologist. The lifestyle intervention included five to six aerobic exercise sessions per week, combined with resistance training two to three times per week and an adjunct dietary intervention aiming at reduction of ∼500 kcal/day (month 0–4). The diet was isocaloric from months 5–12. The primary outcome of this secondary analysis was change in oxidative stress measured by 8-oxo-7,8-dihydroguanosine (8-oxoGuo) and secondarily in 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG), as markers of RNA and DNA oxidation, respectively, from baseline to 12-months follow-up. Results: A total of 77 participants, 21 participants receiving standard care and 56 participants receiving the lifestyle intervention, were included in the analysis. Mean age at baseline was 54.1 years (SD 9.1), 41% were women and mean duration of type 2 diabetes was 5.0 years (SD 2.8). From baseline to follow-up the lifestyle group experienced a 7% decrease in 8-oxoGuo (−0.15 nmol/mmol creatinine [95% CI -0.27, −0.03]), whereas standard care conversely was associated with a 8.5% increase in 8-ox

The diagnosis of COVID-19 is based on detection of SARS-CoV-2 in oro-/nasopharyngel swabs, but due to discomfort and minor risk during the swab procedure, detection of SARS-CoV-2 has been investigated in other biological matrixes. In this proof-of-concept study, individuals with confirmed SARS-CoV-2 infection performed a daily air sample for five days. Air samples were obtained through a non-invasive electrostatic air sampler. Detection of SARS-CoV-2 RNA was determined with qRT-PCR. The association of positive samples with different exposures was evaluated through mixed-effect models. We obtained 665 air samples from 111 included participants with confirmed SARS-CoV-2 infection. Overall, 52 individuals (46.8%) had at least one positive air sample, and 129 (19.4%) air samples were positive for SARS-CoV-2. Participants with symptoms or a symptom duration ≤ four days had significantly higher odds of having a positive air sample. Cycle threshold values were significantly lower in samples obtained ≤ 4 days from symptom onset. Neither variant of SARS-CoV-2 nor method of air sampling were associated with a positive air sample. We demonstrate that SARS-CoV-2 is detectable in human breath by electrostatic air sampling with the highest detection rate closest to symptom onset. We suggest further evaluation of the air sampling technique to increase sensitivity.

Seventy five percent of the world's food crops benefit from insect pollination. Hence, there has been increased interest in how global change drivers impact this critical ecosystem service. Because standardized data on crop pollination are rarely available, we are limited in our capacity to understand the variation in pollination benefits to crop yield, as well as to anticipate changes in this service, develop predictions, and inform management actions. Here, we present CropPol, a dynamic, open, and global database on crop pollination. It contains measurements recorded from 202 crop studies, covering 3,394 field observations, 2,552 yield measurements (i.e., berry mass, number of fruits, and fruit density [kg/ha], among others), and 47,752 insect records from 48 commercial crops distributed around the globe. CropPol comprises 32 of the 87 leading global crops and commodities that are pollinator dependent. Malus domestica is the most represented crop (32 studies), followed by Brassica napus (22 studies), Vaccinium corymbosum (13 studies), and Citrullus lanatus (12 studies). The most abundant pollinator guilds recorded are honey bees (34.22% counts), bumblebees (19.19%), flies other than Syrphidae and Bombyliidae (13.18%), other wild bees (13.13%), beetles (10.97%), Syrphidae (4.87%), and Bombyliidae (0.05%). Locations comprise 34 countries distributed among Europe (76 studies), North America (60), Latin America and the Caribbean (29), Asia (20), Oceania (10), and Africa (7). Sampling spans three decades and is concentrated on 2001–2005 (21 studies), 2006–2010 (40), 2011–2015 (88), and 2016–2020 (50). This is the most comprehensive open global data set on measurements of crop flower visitors, crop pollinators and pollination to date, and we encourage researchers to add more datasets to this database in the future. This data set is released for non-commercial use only. Credits should be given to this paper (i.e., proper citation), and the products generated with this

Metformin and exercise both improve glycemic control, but in vitro studies have indicated that an interaction between metformin and exercise occurs in skeletal muscle, suggesting a blunting effect of metformin on exercise training adaptations. Two studies (a double-blind, parallel-group, randomized clinical trial conducted in 29 glucose-intolerant individuals and a double-blind, cross-over trial conducted in 15 healthy lean males) were included in this paper. In both studies, the effect of acute exercise ± metformin treatment on different skeletal muscle variables, previously suggested to be involved in a pharmaco-physiological interaction between metformin and exercise, was assessed. Furthermore, in the parallel-group trial, the effect of 12 weeks of exercise training was assessed. Skeletal muscle biopsies were obtained before and after acute exercise and 12 weeks of exercise training, and mitochondrial respiration, oxidative stress and AMPK activation was determined. Metformin did not significantly affect the effects of acute exercise or exercise training on mitochondrial respiration, oxidative stress or AMPK activation, indicating that the response to acute exercise and exercise training adaptations in skeletal muscle is not affected by metformin treatment. Further studies are needed to investigate whether an interaction between metformin and exercise is present in other tissues, e.g. the gut. Trial registration: ClinicalTrials.gov (NCT03316690 and NCT02951260).

Seventy five percent of the world's food crops benefit from insect pollination. Hence, there has been increased interest in how global change drivers impact this critical ecosystem service. Because standardized data on crop pollination are rarely available, we are limited in our capacity to understand the variation in pollination benefits to crop yield, as well as to anticipate changes in this service, develop predictions, and inform management actions. Here, we present CropPol, a dynamic, open and global database on crop pollination. It contains measurements recorded from 202 crop studies, covering 3,394 field observations, 2,552 yield measurements (i.e. berry weight, number of fruits and kg per hectare, among others), and 47,752 insect records from 48 commercial crops distributed around the globe. CropPol comprises 32 of the 87 leading global crops and commodities that are pollinator dependent. Malus domestica is the most represented crop (32 studies), followed by Brassica napus (22 studies), Vaccinium corymbosum (13 studies), and Citrullus lanatus (12 studies). The most abundant pollinator guilds recorded are honey bees (34.22% counts), bumblebees (19.19%), flies other than Syrphidae and Bombyliidae (13.18%), other wild bees (13.13%), beetles (10.97%), Syrphidae (4.87%), and Bombyliidae (0.05%). Locations comprise 34 countries distributed among Europe (76 studies), Northern America (60), Latin America and the Caribbean (29), Asia (20), Oceania (10), and Africa (7). Sampling spans three decades and is concentrated on 2001-05 (21 studies), 2006-10 (40), 2011-15 (88), and 2016-20 (50). This is the most comprehensive open global data set on measurements of crop flower visitors, crop pollinators and pollination to date, and we encourage researchers to add more datasets to this database in the future. This data set is released for non-commercial use only. Credits should be given to this paper (i.e., proper citation), and the products generated with this database should

Unhealthy population diets contribute to the burden of non-communicable diseases. Policies targeting food environments (FE policies) may improve population diets. This review of systematic reviews aims to summarise recent evidence of the effectiveness of FE policies in improving diets. We searched PubMed for systematic reviews published from January 2010 onwards. Eligible FE policies included: nutrition and food labelling, provision of foods in public institutions or specific settings, price, marketing, nutrition quality and portion size, and availability of foods in retail and food service establishments. A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR 2) instrument was used to assess review quality. Reviews of critically low quality were excluded. Results were narratively reported in text and tables. The search identified 1102 records after removing duplicates. Following screening and quality assessment we included 12 systematic reviews. Two reviews focused on nutrition and food labelling, two on provision of foods in school settings, four on price, none on marketing policies, three on nutrition quality and portion size and one on the availability of foods in retail and food service establishments. Pricing policies (tax/subsidy) appear effective in altering intake and purchase of targeted foods and beverages. FE policies targeting the availability of foods in retail and food establishments, food provision in school settings, product reformulation and the size of portions/packages or items of tableware also appear effective. Overall, policies targeting food environments appear effective in improving population diets. However, there is a need for further high-quality evidence.

Introduction/Purpose.The increased risk of fractures with type 2 diabetes (T2D) is suggested to be caused by decreased bone turnover. Current international guidelines recommend lifestyle modifications, including exercise, as first-line treatment for T2D. The aim of this study was to investigate the effects of an exercise-based lifestyle intervention on bone turnover and bone mineral density (BMD) in persons with T2D.METHODS: Persons with T2D were randomized to either a 12-months lifestyle intervention (n = 64) or standard care (n = 34). The lifestyle intervention included five to six weekly aerobic training sessions, half of them combined with resistance training. Serum markers of bone turnover (osteocalcin (OC), N-terminal propeptide of type-I procollagen (PINP), reflecting bone formation, and carboxyterminal collagen I crosslinks (CTX-I), reflecting bone resorption) and BMD (by DXA) were measured before the intervention and at follow-up.RESULTS: From baseline to follow-up, s-PINP increased by 34 % (95 % CI: 17 - 50 %), s-CTX-I by 36 % (95 % CI: 1 - 71 %), and s-OC by 31 % (95 % CI: 11 - 51 %) more in the lifestyle intervention group compared with standard care. Loss of weight and fat mass were the strongest mediators of the increased bone turnover. BMD was unaffected by the intervention ([INCREMENT] BMD: 0.1 %, 95 % CI: -1.1 to 1.2 %).CONCLUSIONS: A 12-months intensive exercise-based lifestyle intervention led to a substantial but balanced increase in bone turnover in persons with T2D. The increased bone turnover combined with a preserved BMD, despite a considerable weight loss, is likely to reflect improved bone health and warrants further studies addressing the impact of exercise on risk of fractures in persons with T2D.

Seventy five percent of the world's food crops benefit from insect pollination. Hence, there has been increased interest in how global change drivers impact this critical ecosystem service. Because standardized data on crop pollination are rarely available, we are limited in our capacity to understand the variation in pollination benefits to crop yield, as well as to anticipate changes in this service, develop predictions, and inform management actions. Here, we present CropPol, a dynamic, open and global database on crop pollination. It contains measurements recorded from 202 crop studies, covering 3,394 field observations, 2,552 yield measurements (i.e. berry weight, number of fruits and kg per hectare, among others), and 47,752 insect records from 48 commercial crops distributed around the globe. CropPol comprises 32 of the 87 leading global crops and commodities that are pollinator dependent. Malus domestica is the most represented crop (32 studies), followed by Brassica napus (22 studies), Vaccinium corymbosum (13 studies), and Citrullus lanatus (12 studies). The most abundant pollinator guilds recorded are honey bees (34.22% counts), bumblebees (19.19%), flies other than Syrphidae and Bombyliidae (13.18%), other wild bees (13.13%), beetles (10.97%), Syrphidae (4.87%), and Bombyliidae (0.05%). Locations comprise 34 countries distributed among Europe (76 studies), Northern America (60), Latin America and the Caribbean (29), Asia (20), Oceania (10), and Africa (7). Sampling spans three decades and is concentrated on 2001-05 (21 studies), 2006-10 (40), 2011-15 (88), and 2016-20 (50). This is the most comprehensive open global data set on measurements of crop flower visitors, crop pollinators and pollination to date, and we encourage researchers to add more datasets to this database in the future. This data set is released for non-commercial use only. Credits should be given to this paper (i.e., proper citation), and the products generated with this database should

Antagonistic interactions between the sexes are important drivers of evolutionary divergence. Interlocus sexual conflict is generally described as a conflict between alleles at two interacting loci whose identity and genomic location are arbitrary, but with opposite fitness effects in each sex. We build on previous theory by suggesting that when loci under interlocus sexual conflict are located on the sex chromosomes it can lead to cycles of antagonistic coevolution between them and therefore between the sexes. We tested this hypothesis by performing experimental crosses using Drosophila melanogaster where we reciprocally exchanged the sex chromosomes between five allopatric wild-type populations in a round-robin design. Disrupting putatively coevolved sex chromosome pairs resulted in increased male reproductive success in 16 of 20 experimental populations (10 of which were individually significant), but also resulted in lower offspring egg-to-adult viability that affected both male and female fitness. After 25 generations of experimental evolution these sexually antagonistic fitness effects appeared to be resolved. To formalize our hypothesis, we developed population genetic models of antagonistic coevolution using fitness expressions based on our empirical results. Our model predictions support the conclusion that antagonistic coevolution between the sex chromosomes is plausible under the fitness effects observed in our experiments. Together, our results lend both empirical and theoretical support to the idea that cycles of antagonistic coevolution can occur between sex chromosomes and illustrate how this process, in combination with autosomal coadaptation, may drive genetic and phenotypic divergence between populations.

INTRODUCTION. Hyperglycaemia during hospitalisation is associated with a longer and more complicated admission and with increased mortality. Therefore, guidelines suggest that blood glucose should be less than 10 mmol/l. In this audit, we aimed to describe the prevalence of diabetes patients at four orthopaedic departments in the Capital Region of Denmark and to measure the quality of in-hospital diabetes management. METHODS. We conducted audits of medical records in the electronic health record system for two months in 2019. All patients admitted were included in the audit. We gathered information on diabetes status, orthopaedic diagnosis, glycosylated haemoglobin and diabetes management. RESULTS. Among 2,463 included patients, 10% had diabetes. The three most frequent diagnosis groups were infection, fracture of lower extremity and hospitalised for alloplastic surgery. The number of blood glucose measurements during 24-hour perioperative care was 6.5. Among patients analysed, 10-20% did not have their blood glucose measured in the days following surgery. Among patients, 64% received insulin 1-50% of the required times. CONCLUSION. We demonstrated that 10% of hospitalised patients suffer from diabetes. The audit also showed that blood glucose is generally measured according to guidelines, whereas the treatment of an elevated blood glucose is far from being given according to guidelines. This may potentially delay recovery and prolong hospitalisation. FUNDING. none. TRIAL REGISTRATION. not relevant.

Brain abscesses are often polymicrobial and of unclear primary origin. Here, we compare the use of next-generation sequencing (NGS) technology with classical microbiological diagnostics for identification of clinically relevant microorganisms and describe the microbiome profiling with respect to the primary source of brain abscess. Thirty-six samples from 36 patients, with primary brain abscesses, were subjected to both culture- and 16S/18S rRNA Sanger sequencing-based diagnostics (“standard methods”) and compared to a 16S/18S amplicon-based NGS, which were also subjected to a microbiome diversity analyses. Forty-seven species were identified with “standard methods” compared to 96 species with NGS, both confirming and adding to the number of species identified (p < 0.05). The variation of the brain abscess microbiome diversity was not continuous but could be stratified comparing the presumable origin of infection (“dental,” “sinus,” “disseminated,” or “unknown”). Alpha diversity did not differ (p > 0.05) between groups while beta diversity differed significantly (p = 0.003) comparing disseminated vs the other presumable origin of infection. Interesting, clustering was also detected between “dental” and “sinusitis,” although not significantly (p = 0.07). Microbiome-based diagnostics can increase sensitivity without losing specificity. The bacterial beta diversity differed between the presumably origin of the brain abscess and might help to clarify the primary source of infection.

Introduction: In general, patients with type 2 diabetes have lower cardiorespiratory fitness levels and perform exercise at lower intensities compared to healthy controls. Since metformin (MET) has been shown to increase the rate of perceived exertion (RPE) during exercise with a fixed intensity, MET per se may reduce self-selected exercise intensity. The aim of this study was to assess the effect of MET on self-selected exercise intensity. Methods: Healthy males were eligible for this crossover, counterbalanced study with two treatment periods: MET and placebo (PLA), each lasting 17 days. Treatment dose was gradually increased and reached 2 g/day on treatment day 9, and continued at that level for the rest of the treatment period. The two periods were performed in randomized order. Two experimental days (A+B) were conducted on Day 15 (A) and Day 17 (B) of each period, respectively. Day A consisted of an exercise bout with self-selected exercise intensity (equal to RPE = 14–15 on the Borg Scale). Day B consisted of an exercise bout with fixed intensity (70% of VO2peak). Oxygen consumption rate was assessed continuously during both exercise bouts. Results: Fifteen males (age 23.7 ± 0.6 years, BMI 22.3 ± 2.0, VO2peak 3.5 ± 0.6 L/min) were included in the study. On Day B, RPE was higher in MET compared to PLA (14.8 ± 0.4 vs. 14.0 ± 0.3, P = 0.045). On Day A, no difference in self-selected exercise intensity measured by oxygen consumption rate (PLA 2.33 ± 0.09 L O2/min, MET 2.42 ± 0.10 L O2/min, P = 0.09) was seen between treatment periods. Conclusions: Self-selected exercise intensity was not reduced by MET in healthy males, despite the fact that MET increased RPE during an exercise bout with fixed intensity.

Aims: The once-weekly administered glucagon-like peptide 1 (GLP-1) receptor agonist (GLP-1RA) semaglutide, has, in clinical trials, demonstrated significant reductions in glycated haemoglobin A1c (HbA1c) and body weight in persons with type 2 diabetes. We evaluated the real-world clinical effects of semaglutide once weekly in a hospital-based diabetes out-patient clinic. Methods: This retrospective observational cohort study included persons with type 2 diabetes (n = 119) on a broad range of antidiabetic medicine: GLP-1RA naïve persons (n = 37) and GLP-1RA-experienced persons (n = 82). Person characteristics at inclusion: age [median (quartiles)]: 65 (57, 72) years; body weight 99 (86, 118) kg; body mass index (BMI) 33 (29, 38) kg/m²; HbA1c 61 (54, 69) mmol/mol/(7.7 (7.1, 8.5) %). Data were collected at baseline and after 3, 6 and 12 months of semaglutide treatment. Data were analysed using a general linear mixed model for repeated measurements. Results: After 12 months, the reductions in HbA1c were (mean [95% confidence interval]: GLP-1RA naïve: −12.8 [−17.0, −8.5] mmol/mol/ −1.2 [−1.6, −0.8]% (p < 0.01) and GLP-1RA experienced: −6.4 [−9.0, −3.8] mmol/mol/ −0.6 [−0.8, −0.4]% (p < 0.01), respectively. Body weight reductions in GLP-1RA naïve: −5 [−6.9, −3.1] kg (p < 0.01) and GLP-1RA experienced: −3.2 [−4.4, −2.0] kg (p < 0.01), respectively. Seventy-five percent received 1 mg QW semaglutide. Conclusion: We observed effects of semaglutide once weekly on HbA1c and body weight comparable with the effects observed in clinical studies with fewer persons in our cohort receiving maximum dose of semaglutide.

Functional traits can determine pairwise species interactions, such as those between plants and pollinators. However, the effects of biogeography and evolutionary history on trait-matching and trait-mediated resource specialization remain poorly understood.We compiled a database of 93 mutualistic hummingbird-plant networks (including 181 hummingbird and 1,256 plant species), complemented by morphological measures of hummingbird bill and floral corolla length. We divided the hummingbirds into their principal clades and used knowledge on hummingbird biogeography to divide the networks into four biogeographical regions: Lowland South America, Andes, North & Central America, and the Caribbean islands. We then tested: (a) whether hummingbird clades and biogeographical regions differ in hummingbird bill length, corolla length of visited flowers and resource specialization, and (b) whether hummingbirds' bill length correlates with the corolla length of their food plants and with their level of resource specialization.Hummingbird clades dominated by long-billed species generally visited longer flowers and were the most exclusive in their resource use. Bill and corolla length and the degree of resource specialization were similar across mainland regions, but the Caribbean islands had shorter flowers and hummingbirds with more generalized interaction niches. Bill and corolla length correlated in all regions and most clades, that is, trait-matching was a recurrent phenomenon in hummingbird-plant associations. In contrast, bill length did not generally mediate resource specialization, as bill length was only weakly correlated with resource specialization within one hummingbird clade (Brilliants) and in the regions of Lowland South America and the Andes in which plants and hummingbirds have a long co-evolutionary history. Supplementary analyses including bill curvature confirmed that bill morphology (length and curvature) does not in general predict resource

Indirect interactions are central to ecological and evolutionary dynamics in pollination communities, yet we have little understanding about the processes determining patterns of indirect interactions, such as those between pollinators through shared flowering plants. Instead, research has concentrated on the processes responsible for direct interactions and whole-network structures. This is partly due to a lack of appropriate tools for characterising indirect interaction structures, because traditional network metrics discard much of this information. The recent development of tools for counting motifs (subnetworks depicting interactions between a small number of species) in bipartite networks enables detailed analysis of indirect interaction patterns. Here we generate plant–hummingbird pollination networks based on three major assembly processes—neutral effects (species interacting in proportion to abundance), morphological matching and phenological overlap—and evaluate the motifs associated with each one. We find that different processes produce networks with significantly different patterns of indirect interactions. Neutral effects tend to produce densely connected motifs, with short indirect interaction chains, and motifs where many specialists interact indirectly through a single generalist. Conversely, niche-based processes (morphology and phenology) produced motifs with a core of interacting generalists, supported by peripheral specialists. These results have important implications for understanding the processes determining indirect interaction structures. A free Plain Language Summary can be found within the Supporting Information of this article.

Aims/hypothesis The aim of this parallel-group, double-blinded (study personnel and participants), randomised clinical trial was to assess the interaction between metformin and exercise training on postprandial glucose in glucose-intolerant individuals.Methods Glucose-intolerant (2 h OGTT glucose of 7.8-11.0 mmol/l and/or HbA(1c) of 39-47 mmol/mol [5.7-6.5%] or glucose-lowering-medication naive type 2 diabetes), overweight/obese (BMI 25-42 kg/m(2)) individuals were randomly allocated to a placebo study group (PLA,n = 15) or a metformin study group (MET,n = 14), and underwent 3 experimental days: BASELINE (before randomisation), MEDICATION (after 3 weeks of metformin [2 g/day] or placebo treatment) and TRAINING (after 12 weeks of exercise training in combination with metformin/placebo treatment). Training consisted of supervised bicycle interval sessions with a mean intensity of 64% of Watt(max)for 45 min, 4 times/week. The primary outcome was postprandial glucose (mean glucose concentration) during a mixed meal tolerance test (MMTT), which was assessed on each experimental day. For within-group differences, a group x time interaction was assessed using two-way repeated measures ANOVA. Between-group changes of the outcomes at different timepoints were compared using unpaired two-tailed Student'sttests.Results Postprandial glucose improved from BASELINE to TRAINING in both the PLA group and the MET group ( increment PLA: -0.7 [95% CI -1.4, 0.0] mmol/l,p = 0.05 and increment MET: -0.7 [-1.5, -0.0] mmol/l,p = 0.03), with no between-group difference (p = 0.92). In PLA, the entire reduction was seen from MEDICATION to TRAINING (-0.8 [-1.3, -0.1] mmol/l,p = 0.01). Conversely, in MET, the entire reduction was observed from BASELINE to MEDICATION (-0.9 [-1.6, -0.2] mmol/l,p = 0.01). The reductions in mean glucose concentration during the MMTT from BASELINE to TRAINING were dependent on differential time effects: in the PLA group, a decrease was observed at t

Recent years have seen a rise in the role of communities in achieving the global goals of poverty alleviation alongside environmental protection. Simultaneously, it is increasingly recognised that communities are subject to power asymmetries resulting in differential abilities among community members to benefit from the sustainable management of natural resources. Striving to explore community- based resource management from a new angle, this thesis draws on ideas from different fields of study to build a framework highlighting social networks as central to capabilities for sustainable livelihoods. Following a qualitative single- case study design, documentary data describing the strategies of an organisation employing such community-based approaches are analysed through the developed framework in order to illuminate how these reflect the ideas in the literature. It is found that organisations can empower communities through the facilitation of ties necessary for an enabling social environment while further acting as a network tie themselves through which community members can expand their asset bases. In both scenarios, the support of the outside organisation emerges as key so as to circumvent the hurdles rooted in limited capabilities.

A handful of studies have investigated sexually antagonistic constraints on achieving sex-specific fitness optima, although exclusively through male-genome-limited evolution experiments. In this article, we established a female-limited X chromosome evolution experiment, where we used an X chromosome balancer to enforce the inheritance of the X through the matriline, thus removing exposure to male selective constraints. This approach eliminates the effects of sexually antagonistic selection on the X chromosome, permitting evolution toward a single sex-specific optimum. After multiple generations of selection, we found strong evidence that body size and development time had moved toward a female-specific optimum, whereas reproductive fitness and locomotion activity remained unchanged. The changes in body size and development time are consistent with previous results, and suggest that the X chromosome is enriched for sexually antagonistic genetic variation controlling these particular traits. The lack of change in reproductive fitness and locomotion activity could be due to a number of mutually nonexclusive explanations, including a lack of sexually antagonistic variance on the X chromosome for those traits or confounding effects of the use of the balancer chromosome. This study is the first to employ female-genome-limited selection and adds to the understanding of the complexity of sexually antagonistic genetic variation.

The T allele of TCF7L2 rs7903146 is a common genetic variant associated with type 2 diabetes (T2D), possibly by modulation of incretin action. In this study, we evaluated the effect of the TCF7L2 rs7903146 T allele on the incretin effect and other glucometabolic parameters in normal glucose tolerant individuals (NGT) and participants with T2D. The rs7903146 variant was genotyped in cohorts of 61 NGT individuals (23 were heterozygous (CT) or homozygous (TT) T allele carriers) and 43 participants with T2D (20 with CT/TT). Participants were previously examined by an oral glucose tolerance test (OGTT) and a subsequent isoglycemic intravenous glucose infusion (IIGI). The incretin effect was assessed by quantification of the difference in integrated beta cell secretory responses during the OGTT and IIGI. Glucose and hormonal levels were measured during experimental days, and from these, indices of beta cell function and insulin sensitivity were calculated. No genotype-specific differences in the incretin effect were observed in the NGT group (P = 0.70) or the T2D group (P = 0.68). NGT T allele carriers displayed diminished glucose-dependent insulinotropic polypeptide response during OGTT (P = 0.01) while T allele carriers with T2D were characterized by lower C-peptide AUC after OGTT (P = 0.04) and elevated glucose AUC after OGTT (P = 0.04). In conclusion, our findings do not exclude that this specific TCF7L2 variant increases the risk of developing T2D via diminished incretin effect, but genotype-related defects were not detectable in these cohorts.

BACKGROUND: A well-known metabolic side effect from treatment with glucocorticoids is glucocorticoid-induced diabetes mellitus (GIDM). Guidelines on the management of GIDM in hospitalized patients (in the non-critical care setting), recommend initiation of insulin therapy. The scientific basis and evidence for superiority of insulin therapy over other glucose lowering therapies is however poor and associated with episodes of both hypo- and hyperglycaemia. There is an unmet need for an easier, safe and convenient therapy for glucocorticoid-induced diabetes.METHODS: EANITIATE is a Danish, open, prospective, multicenter, randomized (1:1), parallel group study in patients with new-onset diabetes following treatment with glucocorticoids (> 20 mg equivalent prednisolone dose/day) with blinded endpoint evaluation (PROBE design). Included patients are randomized to either a Sodium-Glucose-Cotransporter 2 (SGLT2) inhibitor or neutral protamin Hagedorn (NPH) insulin and followed for 30 days. Blinded continuous glucose monitoring (CGM) will provide data for the primary endpoint (mean daily blood glucose) and on glucose fluctuations in the two treatment arms. Secondary endpoints are patient related outcomes, hypoglycaemia, means and measures of variation for all values and for time specific glucose values. This is a non-inferiority study with the intent to demonstrate that treatment with empagliflozin is not inferior to treatment with NPH insulin when it comes to glycemic control and side effects.DISCUSSION: This novel approach to management of glucocorticoid-induced hyperglycemia has not been tested before and if SGLT2 inhibition with empaglifozin compared to NPH-insulin is a safe, effective and resource sparing treatment for GIDM, it has the potential to improve the situation for affected patients and have health economic benefits.TRIAL REGISTRATION: www.clinicaltrialsregister.eu no.: 2018-002640-82. Prospectively registered November 20th. 2018. Dat

Aims/hypothesis The aim was to investigate whether an intensive lifestyle intervention, with high volumes of exercise, improves beta cell function and to explore the role of low-grade inflammation and body weight.Methods This was a randomised, assessor-blinded, controlled trial. Ninety-eight individuals with type 2 diabetes (durationResults At baseline, individuals were 54.8 years (SD 8.9), 47% women, type 2 diabetes duration 5 years (IQR 3-8) and HbA(1c)was 49.3 mmol/mol (SD 9.2); 6.7% (SD 0.8). The intensive lifestyle group showed 40% greater improvement in the disposition index compared with the standard care group (ratio of geometric mean change [RGM] 1.40 [95% CI 1.01, 1.94]) from baseline to 12 months' follow-up. Plasma concentration of IL-1 receptor antagonist (IL-1ra) decreased 30% more in the intensive lifestyle group compared with the standard care group (RGM 0.70 [95% CI 0.58, 0.85]). Statistical single mediation analysis estimated that the intervention effect on the change in IL-1ra and the change in body weight explained to a similar extent (59%) the variance in the intervention effect on the disposition index.Conclusions/interpretation Our findings show that incorporating an intensive lifestyle intervention, with high volumes of exercise, in individuals with type 2 diabetes has the potential to improve beta cell function, associated with a decrease in low-grade inflammation and/or body weight.

Pollination by wild pollinators is a key ecosystem service threatened by anthropogenic-induced land-use change. The proximity to natural habitat has previously been shown to positively affect pollinator communities and improve crop yield and quality but empirical evidence is limited from most parts of the World. Here, across six farms in Southern Thailand, we investigated the significance of landscape-level effects of natural habitat (proportion of and distance to evergreen forest) on both visitation rate and richness of pollinators as well as fruit set of guava (Psidium guajava L.), a local economically-important crop in the tropics. Overall, the most abundant pollinator was the Asian honey bee Apis cerana (39% of all visits) and different species of stingless bees (37%). We found that pollinator richness was unrelated to the proportion and distance to evergreen forest, however, the proportion of forest within a 1, 5 and 10 km radius had a significant positive impact on visitation rate of wild pollinators. Still, neither the various forest parameters nor pollinator visitation rate showed a significant impact on fruit set of guava, perhaps because guava self-pollinates. This illustrates that landscape-level degradation of natural habitat may negatively impact pollinator communities without diminishing the crop yield of the farmers.

BACKGROUND: There is an ongoing discussion on whether routinely patch testing with p-phenylenediamine (PPD) 1.0% pet. is safe, owing to the risk of patch test sensitization. Late-appearing patch test reactions may reflect patch test sensitization, but may also be attributable to a low degree of pre-existing sensitization.OBJECTIVES: To follow the positive patch test reactions to PPD and its salt PPD dihydrochloride (PPD-DHC) in order to characterize reaction patterns concerning time and dose in PPD-sensitized individuals.METHODS: Volunteers with previous reactions to PPD 1.0% were included and patch tested with PPD and PPD-DHC in equimolar dilution series. There were then seven follow-up visits over a period of 28 days.RESULTS: Twenty-six volunteers completed the study, of whom 23 of 26 (88%) reacted to PPD 1.0%, and 69% reacted to PPD 0.32%. Altogether, 42% and 27% reacted to the corresponding equimolar concentrations of PPD-DHC. After day 7, no new reactions were observed to any concentration tested, either of PPD or of PPD-DHC.CONCLUSION: No late-appearing reactions to PPD or PPD-DHC were observed at any dose. There is a risk of missing contact allergy when the dose is decreased.

Pivmecillinam (amdinocillin pivoxil) is the recommended first-choice antibiotic used to treat urinary tract infections (UTIs) in Denmark. The frequency of mutation to mecillinam (MEC) resistance is described as high in vitro; however, treatment of UTI has a good clinical response and prevalence of mecillinam resistance in Escherichia coli remains low despite many years of use. We describe occurrence of in vivo mecillinam resistance in a clinical isolate of ESBL-producing E. coli following pivmecillinam treatment. The identified phenotypic differences in the mecillinam resistant isolate compared with the original mecillinam susceptible isolate were a full-length LPS with O-antigen (O25), mecillinam resistance and a lower MIC for ceftazidime. Regarding genotype, the resistant isolate differed with a mutation in blaCTX-M-15 to blaCTX-M-127 , loss of a part of a plasmid and a genomic island, respectively, and insertion of a transposase in wbbL, causing the rough phenotype. The observed mecillinam resistance is expected to be caused by the mutation in blaCTX-M-15 with additional contribute from the serotype shift. We continue to recommend the use of pivmecillinam as first-line treatment for UTI.

Filip Jansåker,1,2 Jonas Bredtoft Boel,3 Sara Thønnings,1,2 Frederik Boëtius Hertz,3 Katrine Hartung Hansen,2 Niels Frimodt-Møller,2 Jenny Dahl Knudsen1,21Department of Clinical Microbiology, Hvidovre Hospital, University of Copenhagen, 2650 Hvidovre, Denmark; 2Department of Clinical Microbiology, Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark; 3Department of Clinical Microbiology, Herlev and Gentofte Hospital, University of Copenhagen, 2730 Herlev, DenmarkObjectives: To compare the therapeutic effect of pivmecillinam and other common oral antibiotics for community-acquired urinary tract infections (UTIs) caused by Extended Spectrum Beta-Lactamase (ESBL)- or non-ESBL-producing Escherichia coli.Methods: Retrospective cohort study from 2010 to mid-2016 with data from the regional Laboratory Database and three national databases on antibiotic prescriptions, hospital admission, and mortality, respectively. Primary care patients (≥18 years) empirically treated for UTI caused by non-ESBL- or ESBL-producing E. coli (non-ESBL and ESBL E. coli) were included. Seven antibiotics, commonly used empirically for UTI, were investigated. Treatment failure measured as the redemption of a new antibiotic prescription or admission to hospital due to UTI. Cox proportional hazard ratios and adjusted risk differences along with 95% confidence intervals were calculated for 14 and 30 days, respectively.Results: Thirty-six thousand two hundred and ninety-three (95.7%) and 1624 (4.3%) cases were included in the non-ESBL and ESBL groups, respectively. Male sex, high age, ESBL production, and resistance to empirical therapy were found to independently increase the risk of treatment failure. Compared to pivmecillinam, ciprofloxacin had significantly lower treatment failure for non-ESBL E. coli, but significantly higher treatment failure in ESBL E. coli. There was no significant difference between nitrofurantoin and pivmecillinam