The state of the art in beyond 5G distributed massive multiple-input multiple-output communication system solutions.

Beyond fifth generation (5G) communication systems aim towards data rates in the tera bits per second range, with improved and flexible coverage options, introducing many new technological challenges in the fields of network architecture, signal pro- cessing, and radio frequency front-ends. One option is to move towards cell-free, or distributed massive Multiple-Input Multiple-Output (MIMO) network architectures and highly integrated front-end solutions. This paper presents an outlook on be- yond 5G distributed massive MIMO communication systems, the signal processing, characterisation and simulation challenges, and an overview of the state of the art in millimetre wave antennas and electronics.

Framework for the environmental impact assessment of operational shipping.

Shipping is an important source of pollution affecting both atmospheric and aquatic environments. To allow for efficient mitigation of environmental degradation, it is essential to know the extent of the impacts of shipping in relation to other sources of pollution. Here, we give a perspective on a holistic approach to studies of the environmental impacts of operational shipping through presentation of an assessment framework developed and applied on a case of shipping in the Baltic Sea. Through transfer of knowledge and concepts, previously used in assessments of air pollution, now applied to assessments of marine pollution and underwater noise, the horizon of understanding of shipping-related impacts is significantly improved. It identifies the main areas of environmental degradation caused by shipping and potential improvements through legislation and technological development. However, as the vast majority of contaminants discharged into the sea are not routinely monitored and assessed, the links between pressure of contaminants from shipping and environmental state and impacts will not be caught in the current environmental regulatory frameworks.

A comprehensive survey of integron-associated genes present in metagenomes.

BACKGROUND: Integrons are genomic elements that mediate horizontal gene transfer by inserting and removing genetic material using site-specific recombination. Integrons are commonly found in bacterial genomes, where they maintain a large and diverse set of genes that plays an important role in adaptation and evolution. Previous studies have started to characterize the wide range of biological functions present in integrons. However, the efforts have so far mainly been limited to genomes from cultivable bacteria and amplicons generated by PCR, thus targeting only a small part of the total integron diversity. Metagenomic data, generated by direct sequencing of environmental and clinical samples, provides a more holistic and unbiased analysis of integron-associated genes. However, the fragmented nature of metagenomic data has previously made such analysis highly challenging. RESULTS: Here, we present a systematic survey of integron-associated genes in metagenomic data. The analysis was based on a newly developed computational method where integron-associated genes were identified by detecting their associated recombination sites. By processing contiguous sequences assembled from more than 10 terabases of metagenomic data, we were able to identify 13,397 unique integron-associated genes. Metagenomes from marine microbial communities had the highest occurrence of integron-associated genes with levels more than 100-fold higher than in the human microbiome. The identified genes had a large functional diversity spanning over several functional classes. Genes associated with defense mechanisms and mobility facilitators were most overrepresented and more than five times as common in integrons compared to other bacterial genes. As many as two thirds of the genes were found to encode proteins of unknown function. Less than 1% of the genes were associated with antibiotic resistance, of which several were novel, previously undescribed, resistance gene variants. CONCLUSIONS: Our results highlight the large functional diversity maintained by integrons present in unculturable bacteria and significantly expands the number of described integron-associated genes.

Shipborne nutrient dynamics and impact on the eutrophication in the Baltic Sea.

The Baltic Sea is a severely eutrophicated sea-area where intense shipping as an additional nutrient source is a potential contributor to changes in the ecosystem. The impact of the two most important shipborne nutrients, nitrogen and phosphorus, on the overall nutrient-phytoplankton-oxygen dynamics in the Baltic Sea was determined by using the coupled physical and biogeochemical model system General Estuarine Transport Model-Ecological Regional Ocean Model (GETM-ERGOM) in a cascade with the Ship Traffic Emission Assessment Model (STEAM) and the Community Multiscale Air Quality (CMAQ) model. We compared two nutrient scenarios in the Baltic Sea: with (SHIP) and without nutrient input from ships (NOSHIP). The model uses the combined nutrient input from shipping-related waste streams and atmospheric depositions originating from the ship emission and calculates the effect of excess nutrients on the overall biogeochemical cycle, primary production, detritus formation and nutrient flows. The shipping contribution is about 0.3% of the total phosphorus and 1.25-3.3% of the total nitrogen input to the Baltic Sea, but their impact to the different biogeochemical variables is up to 10%. Excess nitrogen entering the N-limited system of the Baltic Sea slightly alters certain pathways: cyanobacteria growth is compromised due to extra nitrogen available for other functional groups while the biomass of diatoms and especially flagellates increases due to the excess of the limiting nutrient. In terms of the Baltic Sea ecosystem functioning, continuous input of ship-borne nitrogen is compensated by steady decrease of nitrogen fixation and increase of denitrification, which results in stationary level of total nitrogen content in the water. Ship-borne phosphorus input results in a decrease of phosphate content in the water and increase of phosphorus binding to sediments. Oxygen content in the water decreases, but reaches stationary state eventually.

Metaxa2 Database Builder: enabling taxonomic identification from metagenomic or metabarcoding data using any genetic marker.

Motivation: Correct taxonomic identification of DNA sequences is central to studies of biodiversity using both shotgun metagenomic and metabarcoding approaches. However, no genetic marker gives sufficient performance across all the biological kingdoms, hampering studies of taxonomic diversity in many groups of organisms. This has led to the adoption of a range of genetic markers for DNA metabarcoding. While many taxonomic classification software tools can be re-trained on these genetic markers, they are often designed with assumptions that impair their utility on genes other than the SSU and LSU rRNA. Here, we present an update to Metaxa2 that enables the use of any genetic marker for taxonomic classification of metagenome and amplicon sequence data. Results: We evaluated the Metaxa2 Database Builder on 11 commonly used barcoding regions and found that while there are wide differences in performance between different genetic markers, our software performs satisfactorily provided that the input taxonomy and sequence data are of high quality. Availability and implementation: Freely available on the web as part of the Metaxa2 package at http://microbiology.se/software/metaxa2/. Supplementary information: Supplementary data are available at Bioinformatics online.

Intellectual disability in children aged less than seven years born moderately and late preterm compared with very preterm and term-born children - a nationwide birth cohort study.

BACKGROUND: Prematurity has been shown to be associated with an increased risk of intellectual disability (ID). METHOD: The aim was to establish whether the prevalence of ID, defined as significant limitations in both intellectual (intelligence quotient below 70) and adaptive functioning among moderately preterm (MP; 32+0 -33+6  weeks) and late preterm (LP; 34+0 -36+6  weeks) infants, is increased compared with that in term infants (≥37+0  weeks). Antenatal and neonatal risk factors for ID among gestational age groups were sought. The national register study included all live-born infants in Finland in 1991-2008, excluding those who died before one year age, or had any major congenital anomaly or missing data. A total of 1 018 256 infants (98.0%) were analysed: very preterm (VP; <32+0  weeks, n = 6329), MP (n = 6796), LP (n = 39 928) and term (n = 965 203). RESULTS: By the age of seven years, the prevalence of ID was 2.48% in the VP group, 0.81% in the MP group, 0.55% in the LP group and 0.35% in the term group. Intracranial haemorrhage increased the ID risk in all groups. Male sex and born small for gestational age predicted an increased risk in all but the MP group. CONCLUSIONS: The prevalence of ID decreased with increasing gestational age. Prevention of intracranial haemorrhages may have a beneficial effect on the neurodevelopmental outcomes of neonates.

Comparison of four DNA extraction methods for comprehensive assessment of 16S rRNA bacterial diversity in marine biofilms using high-throughput sequencing.

High-throughput DNA sequencing technologies are increasingly used for the metagenomic characterisation of microbial biodiversity. However, basic issues, such as the choice of an appropriate DNA extraction method, are still not resolved for non-model microbial communities. This study evaluates four commonly used DNA extraction methods for marine periphyton biofilms in terms of DNA yield, efficiency, purity, integrity and resulting 16S rRNA bacterial diversity. Among the tested methods, the Plant DNAzol® Reagent (PlantDNAzol) and the FastDNA® SPIN Kit for Soil (FastDNA Soil) methods were best suited to extract high quantities of DNA (77-130 µg g wet wt-1). Lower amounts of DNA were obtained (<37 µg g wet wt-1) with the Power Plant® Pro DNA Isolation Kit (PowerPlant) and the Power Biofilm® DNA Isolation Kit (PowerBiofilm) methods, but integrity and purity of the extracted DNA were higher. Results from 16S rRNA amplicon sequencing demonstrate that the choice of a DNA extraction method significantly influences the bacterial community profiles generated. A higher number of bacterial OTUs were detected when DNA was extracted with the PowerBiofilm and the PlantDNAzol methods. Overall, this study demonstrates the potential bias in metagenomic diversity estimates associated with different DNA extraction methods.

Safety and efficacy of the combination of pegylated interferon-α2b and dasatinib in newly diagnosed chronic-phase chronic myeloid leukemia patients.

Dasatinib (DAS) and interferon-α have antileukemic and immunostimulatory effects and induce deep responses in chronic myeloid leukemia (CML). We assigned 40 newly diagnosed chronic-phase CML patients to receive DAS 100 mg o.d. followed by addition of pegylated interferon-α2b (PegIFN) after 3 months (M3). The starting dose of PegIFN was 15 µg/week and it increased to 25 µg/week at M6 until M15. The combination was well tolerated with manageable toxicity. Of the patients, 84% remained on PegIFN at M12 and 91% (DAS) and 73% (PegIFN) of assigned dose was given. Only one patient had a pleural effusion during first year, and three more during the second year. After introduction of PegIFN we observed a steep increase in response rates. Major molecular response was achieved in 10%, 57%, 84% and 89% of patients at M3, M6, M12 and M18, respectively. At M12, MR(4) was achieved by 46% and MR(4.5) by 27% of patients. No patients progressed to advanced phase. In conclusion, the combination treatment appeared safe with very promising efficacy. A randomized comparison of DAS±PegIFN is warranted.

Minimal selective concentrations of tetracycline in complex aquatic bacterial biofilms.

Selection pressure generated by antibiotics released into the environment could enrich for antibiotic resistance genes and antibiotic resistant bacteria, thereby increasing the risk for transmission to humans and animals. Tetracyclines comprise an antibiotic class of great importance to both human and animal health. Accordingly, residues of tetracycline are commonly detected in aquatic environments. To assess if tetracycline pollution in aquatic environments promotes development of resistance, we determined minimal selective concentrations (MSCs) in biofilms of complex aquatic bacterial communities using both phenotypic and genotypic assays. Tetracycline significantly increased the relative abundance of resistant bacteria at 10 µg/L, while specific tet genes (tetA and tetG) increased significantly at the lowest concentration tested (1 µg/L). Taxonomic composition of the biofilm communities was altered with increasing tetracycline concentrations. Metagenomic analysis revealed a concurrent increase of several tet genes and a range of other genes providing resistance to different classes of antibiotics (e.g. cmlA, floR, sul1, and mphA), indicating potential for co-selection. Consequently, MSCs for the tet genes of ≤ 1 µg/L suggests that current exposure levels in e.g. sewage treatment plants could be sufficient to promote resistance. The methodology used here to assess MSCs could be applied in risk assessment of other antibiotics as well.

Reconstructive vascular surgery and the extent of tissue damage due to diabetic foot ulcers relates to risk of new ulceration in patients with PAD.

OBJECTIVE: There is limited information regarding new ulceration following the healing of ischaemic foot ulcers in diabetic patients. Our aim is to study new ulcerations in the same foot as the previous ulcer(s) in patients with diabetes and severe peripheral artery disease (PAD). METHOD: Patients with diabetes and severe PAD who healed from previous ulcer(s) (Wagner grade 1-5, at or below the ankle), were recruited for the prospective study from the time of healing of their ulcer. Patients were followed up regarding new ulceration, and their treatments and ulcer status noted either directly or on examination of medical records. RESULTS: We analysed the data on 602 patients with diabetes and severe PAD with healed foot ulcers, either primarily (n=443, 74%) or after minor amputation (n=159, 26%). Of these 51% (n=305) had revascularisation before healing from the previous ulcer, 34% (n=202) developed a new ulcer on the same foot within 15 months (range 0-106). Amputation was required by 22% (n=45) of patients, with a new ulcer on the same foot. The median survival time of all patients (n=602) was 54 months. By regression analysis, a low maximal Wagner grade for the previous ulcer and reconstructive vascular surgery was related to a decreased risk of developing new ulcers in the same foot. CONCLUSION: Patients with diabetes and ischaemic foot ulcers have a high-risk for developing new ulcers and amputation in the same foot after healing. The extent of tissue involvement in the previous ulcer and reconstructive vascular surgery affected the risk for development of new ulcers.

Less pronounced response to exercise in healthy relatives to type 2 diabetic subjects compared with controls.

Healthy first-degree relatives with heredity of type 2 diabetes (FH+) are known to have metabolic inflexibility compared with subjects without heredity for diabetes (FH-). In this study, we aimed to test the hypothesis that FH+ individuals have an impaired response to exercise compared with FH-. Sixteen FH+ and 19 FH- insulin-sensitive men similar in age, peak oxygen consumption (V̇o2 peak), and body mass index completed an exercise intervention with heart rate monitored during exercise for 7 mo. Before and after the exercise intervention, the participants underwent a physical examination and tests for glucose tolerance and exercise capacity, and muscle biopsies were taken for expression analysis. The participants attended, on average, 39 training sessions during the intervention and spent 18.8 MJ on exercise. V̇o2 peak/kg increased by 14%, and the participants lost 1.2 kg of weight and 3 cm waist circumference. Given that the FH+ group expended 61% more energy during the intervention, we used regression analysis to analyze the response in the FH+ and FH- groups separately. Exercise volume had a significant effect on V̇o2 peak, weight, and waist circumference in the FH- group, but not in the FH+ group. After exercise, expression of genes involved in metabolism, oxidative phosphorylation, and cellular respiration increased more in the FH- compared with the FH+ group. This suggests that healthy, insulin-sensitive FH+ and FH- participants with similar age, V̇o2 peak, and body mass index may respond differently to an exercise intervention. The FH+ background might limit muscle adaptation to exercise, which may contribute to the increased susceptibility to type 2 diabetes in FH+ individuals.

Long-term effects of the antibacterial agent triclosan on marine periphyton communities.

Triclosan is a widely used antibacterial agent that has become a ubiquitous contaminant in freshwater, estuary, and marine environments. Concerns about potential adverse effects of triclosan have been described in several recent risk assessments. Its effects on freshwater microbial communities have been well studied, but studies addressing effects on marine microbial communities are scarce. In the present study, the authors describe short- and long-term effects of triclosan on marine periphyton (microbial biofilm) communities. Short-term effects on photosynthesis were estimated after 60 min to 210 min of exposure. Long-term effects on photosynthesis, chlorophyll a fluorescence, pigment content, community tolerance, and bacterial carbon utilization were studied after exposing periphyton for 17 d in flow-through microcosms to 0.316 nM to 10,000 nM triclosan. Results from the short-term studies show that triclosan is toxic to periphyton photosynthesis. Half maximal effective concentration (EC50) values of 1080 nM and 3000 nM were estimated using (14)CO2-incorporation and pulse amplitude modulation (PAM) fluorescence measurements, respectively. After long-term triclosan exposure in flow-through microcosms, photosynthesis estimated using PAM fluorometry was not inhibited by triclosan concentrations up to 1000 nM but instead increased with increasing triclosan concentration. Similarly, at exposure concentrations of 31.6 nM and higher, triclosan caused an increase in photosynthetic pigments. At 316 nM triclosan, the pigment amounts were increased by a factor of 1.4 to 1.9 compared with the control level. Pollution-induced community tolerance was observed for algae and cyanobacteria at 100 nM triclosan and higher. Despite the widespread use of triclosan as an antibacterial agent, the compound did not have any effects on bacterial carbon utilization after long-term exposure.

Lifestyle habits and fatigue among people with systemic lupus erythematosus and matched population controls.

OBJECTIVE: The objective of this paper is to identify clusters of fatigue in patients with systemic lupus erythematosus (SLE) and matched controls, and to analyze these clusters with respect to lifestyle habits, health-related quality of life (HRQoL), anxiety and depression. METHODS: Patients with SLE (n = 305) and age- and gender-matched population controls (n = 311) were included. Three measurements of fatigue (Fatigue Severity Scale (FSS), Vitality (VT, from SF-36) and Multidimensional Assessment of Fatigue scale (MAF) and hierarchic cluster analysis were used to define clusters with different degrees of fatigue. Lifestyle habits were investigated through questionnaires. HRQoL was assessed with the SF-36 and anxiety/depression with the Hospital Anxiety and Depression Scale. RESULTS: Three clusters, denominated "High," "Intermediate" and "Low" fatigue clusters, were identified. The "High" contained 80% patients, and 20% controls (median; VT 25, FSS 5.8, MAF 37.4). These had the most symptoms of depression (51%) and anxiety (34%), lowest HRQoL (p < 0.001) and they exercised least frequently. The "Intermediate" (48% patients and 52% controls) (median; VT 55, FSS 4.1, MAF 23.5) had similarities with the "Low" regarding sleep/rest whereas social status and smoking were closer to the "High." The"Low" contained 22% patients and 78% controls (median; VT 80, FSS 2.3, MAF 10.9). They had the highest perceived HRQoL (p < 0.001), least symptoms of anxiety (10%), no depression, smoked least (13%) and reported the highest percentage (24%) of exercising ≥ 3 times/week. CONCLUSION: Fatigue is common, but not a general feature of SLE. It is associated with depression, anxiety, low HRQoL and less physical exercise. Patients with SLE and population controls with a healthy lifestyle reported lower levels of fatigue. Whether lifestyle changes can reduce fatigue, which is a major problem for a majority of SLE patients, needs to be further explored.

Early revascularization after admittance to a diabetic foot center affects the healing probability of ischemic foot ulcer in patients with diabetes.

OBJECTIVES: There is limited information about whether time from recognition of decreased perfusion to revascularization affects the probability of healing in a patient with a diabetic foot ulcer. The aim of the present study was to examine whether time to revascularization after referral to a multidisciplinary foot center was related to the outcome of foot ulcers in patients with diabetes and severe peripheral arterial disease (PAD). METHODS: Patients with diabetes, a foot ulcer, and a systolic toe pressure <45 mmHg or an ankle pressure <80 mmHg were prospectively included at the foot center, and considered for revascularization according to a preset protocol. All patients underwent invasive revascularization, either percutaneous transluminal angioplasty (PTA) or reconstructive vascular surgery. All patients had continuous follow-up until healing or death irrespective of the type of revascularization. RESULTS: A total of 478 patients were included (age 74 [range 66-80] years, 60% males), of whom 315 patients (66%) had PTA, and 163 (34%) had reconstructive surgery. Of the 478 patients, 217 (45%) healed primarily, 88 (19%) healed after a minor amputation, 76 (16%) healed after a major amputation and 92 patients (19%) died unhealed. The median time from inclusion in the study to revascularization was 8 weeks (3-18 weeks). Time to vascular intervention within 8 weeks (p < .001), maximum Wagner grade reached <3 (p < .001), absence of peripheral edema (p = .033), and presence of intermittent claudication (p = .001) were related to a higher probability of healing. CONCLUSIONS: Time to revascularization and extent of tissue damage were related to the probability of healing of ischemic foot ulcer in patients with diabetes over time. In the presence of a decreased perfusion in a patient with diabetes and a foot ulcer not only revascularization per se but also timing of revascularization is important for the possibility of healing without a major amputation.

Extensive changes in the transcriptional profile of human adipose tissue including genes involved in oxidative phosphorylation after a 6-month exercise intervention.

AIM: Adipose tissue has an important function in total energy homeostasis, and its dysregulation may contribute to lifestyle-related diseases such as type 2 diabetes, cancer and cardiovascular diseases. The aim of this study was to investigate genome-wide mRNA expression in adipose tissue in healthy men before and after an exercise intervention to identify genes or pathways that mediate the beneficial effect of regular exercise. We also investigated the difference in adipose tissue mRNA expression between individuals with or without a family history of type 2 diabetes. METHODS: The 6-month supervised exercise intervention was conducted in 47 healthy men (age 37.8 ± 4.3 years, BMI 28.5 ± 3.6 kg m(-2) ) with a previous low level of physical activity. RNA was analysed using GeneChip Human Gene 1.0 ST arrays (Affymetrix) before and after the exercise. RESULTS: We identified 2,560 significant transcripts differentially expressed before vs. after exercise with a false discovery rate (FDR) < 0.1%, including genes encoding the respiratory chain, histone subunits, small nucleolar RNAs and ribosomal proteins. Additionally, pathways enriched in response to exercise include the ribosome, oxidative phosphorylation, proteasome and many metabolic pathways, whereas the WNT and MAPK signalling pathways were down-regulated (FDR < 5%) after exercise. There were no significant differences in mRNA expression between individuals with or without a family history of type 2 diabetes. CONCLUSION: Exercise increased the expression of genes involved in oxidative phosphorylation, which is the opposite of what has been seen in adipose tissue from elderly or obese individuals with low physical fitness, and our study thereby demonstrates a mechanism for the beneficial effect of exercise.

Outcome of ischemic foot ulcer in diabetic patients who had no invasive vascular intervention.

OBJECTIVE/BACKGROUND: There is limited information regarding outcome in patients not available for revascularisation. Our aim was to identify factors related to ulcer healing in diabetic patients with severe peripheral arterial disease who were not available for revascularisation. METHODS: Diabetic patients with a foot ulcer, consecutively presenting at a multidisciplinary foot centre with systolic toe pressure <45 mmHg or an ankle pressure <80 mmHg were prospectively included. Patients who received revascularisation were excluded. All patients had continuous follow-up until healing or death. RESULTS: Out of 602 patients (median age: 76 years) included in this study, 50% healed either primarily (76%) or with a minor amputation (24%). Seventeen percent of patients healed after major amputation and 33% died unhealed. By regression analysis, rest pain, impaired renal function, ischemic heart disease, cerebral vascular disease, extent of tissue destruction, and ankle pressure >50 mmHg affected the outcome of the ulcers. CONCLUSION: Diabetic patients with ischemic foot ulcers not available for revascularisations are not excluded from healing without major amputation. Factors strongly related to outcome were co-morbidity, severity of peripheral arterial disease, and extent of tissue destruction. Our findings reinforce the need for a classification system considering these factors at decision-making for vascular intervention.

Telomere length in blood and skeletal muscle in relation to measures of glycaemia and insulinaemia.

AIMS: Skeletal muscle is a major metabolic organ and plays important roles in glucose metabolism, insulin sensitivity and insulin action. Muscle telomere length reflects the myocyte's exposure to harmful environmental factors. Leukocyte telomere length is considered a marker of muscle telomere length and is used in epidemiologic studies to assess associations with ageing-related diseases where muscle physiology is important. However, the extent to which leucocyte and muscle telomere length are correlated is unknown, as are their relative correlations with glucose and insulin concentrations. The purpose of this study was to determine the extent of these relationships. METHODS: Leucocyte and muscle telomere length were measured by quantitative real-time polymerase chain reaction in participants from the Malmö Exercise Intervention (n = 27) and the Prevalence, Prediction and Prevention of Diabetes-Botnia studies (n = 31). Participants in both studies were free from Type 2 diabetes. We assessed the association between leucocyte telomere length, muscle telomere length and metabolic traits using Spearmen correlations and multivariate linear regression. Bland-Altman analysis was used to assess agreement between leucocyte and muscle telomere length. RESULTS: In age-, study-, diabetes family history- and sex-adjusted models, leucocyte and muscle telomere length were positively correlated (r = 0.39, 95% CI 0.15-0.59). Leucocyte telomere length was inversely associated with 2-h glucose concentrations (r = -0.58, 95% CI -1.0 to -0.16), but there was no correlation between muscle telomere length and 2-h glucose concentrations (r = 0.05, 95% CI -0.35 to 0.46) or between leucocyte or muscle telomere length with other metabolic traits. CONCLUSIONS: In summary, the current study supports the use of leucocyte telomere length as a proxy for muscle telomere length in epidemiological studies of Type 2 diabetes aetiology.

Megraft: a software package to graft ribosomal small subunit (16S/18S) fragments onto full-length sequences for accurate species richness and sequencing depth analysis in pyrosequencing-length metagenomes and similar environmental datasets.

Metagenomic libraries represent subsamples of the total DNA found at a study site and offer unprecedented opportunities to study ecological and functional aspects of microbial communities. To examine the depth of a community sequencing effort, rarefaction analysis of the ribosomal small subunit (SSU/16S/18S) gene in the metagenome is usually performed. The fragmentary, non-overlapping nature of SSU sequences in metagenomic libraries poses a problem for this analysis, however. We introduce a software package - Megraft - that grafts SSU fragments onto full-length SSU sequences, accounting for observed and unobserved variability, for accurate assessment of species richness and sequencing depth in metagenomics endeavors.