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ObjectiveTo study the time-dependent changes in disease features of Danish patients with acromegaly, including treatment modalities, biochemical outcome, and comorbidities, with a particular focus on cancer and mortality.MethodsPertinent acromegaly-related variables were collected from 739 patients diagnosed since 1990. Data are presented across three decades (1990–1999, 2000–2009, and 2010–2021) based on the year of diagnosis or treatment initiation.ResultsAdenoma size and insulin-like growth factor I (IGF-I) levels at diagnosis did not differ significantly between study periods. The risk of being diagnosed with diabetes, heart disease, sleep apnea, joint disease, and osteoporosis increased from the 1990s to the later decades, while the mortality risk declined to nearly half. The risk of cancer did not significantly change. Treatment changed toward the use of more medical therapy, and fewer patients underwent repeat surgeries or pituitary irradiation. A statistically significant increase in the proportion of patients achieving IGF-I normalization within 3–5 years was observed over time (69%, 83%, and 88%). The proportion of patients with three or more deficient pituitary hormones decreased significantly over time.ConclusionModern medical treatment regimens of acromegaly as well as increased awareness and improved diagnostics for its comorbidities have led to better disease control, fewer patients with severe hypopituitarism, and declining mortality in the Danish cohort of acromegaly patients. The risk of cancer did not increase over the study period.

Several studies have shown that attendance rates are lower among non-Western immigrants than among natives. As the Nordic countries have quite similar health systems and populations but also differences in the organisation of their organised mammography screening programmes, differences in attendance rates could highlight organisational factors that might increase the attendance rates. Mammography screening is offered free of charge in Denmark and Finland, but not in Iceland and Norway. Contrarily to the other countries, Iceland do not send out pre-booked appointment.The study population included natives and non-Western immigrants aged 50–69 years, who had at least one invitation to the national mammography screening programmes in Denmark (2008–2017), Finland (2001–2017), Iceland (2001–2020) or Norway (2001–2015). Relative risks (RRs) of attendance were estimated and adjusted for age group and calendar period.The study population included 116.033 non-Western immigrants and more than 2 million natives. The attendance rates were significantly lower among non-Western immigrants than among natives, with an adjusted relative risk of 0.81/0.80 in Denmark and Finland, 0.62 in Norway, and 0.40 in Iceland. The lower attendance rates among immigrants in Norway and Iceland did not seem to be due to differences in birth country, immigration age, or educational level, but might be explained by organisational factors.Offering free-of-charge mammography screening in Norway and Iceland and/or including a pre-booked appointment in the invitation letters in Iceland might increase the attendance rate among non-Western immigrants.

Agricultural industries rely on physical fences to manage livestock. However, these present practical, financial, and ecological challenges, which may be solved using virtual fencing. This study aimed to identify how experienced cattle through social facilitation and the introduction method influence inexperienced cattle. Based on three stocks held in Fanø, Denmark, containing 12, 17 and 13 Angus (Bos taurus), we examined the virtual fence learning in three case studies using one gradual introduction with zero experienced cattle (A) and two different instant introductions with one (B) and ten (C) experienced cattle. Gradual introduction had the virtual fence moved 20 m every other day for eleven days, and in the two instant introductions, the physical fence was removed in one day. Warnings and impulses were recorded during an 11-day learning period and a 26-day post-learning period, using the impulses per warning to quantify if the cattle adapted. Case studies A and B showed a significant reduction in the warnings and impulses, but only A showed a significant reduction in the impulses per warning when comparing the learning period to the post-learning period. Due to the non-standardised experiments, it was not possible to conclude if the number of experienced cattle or the introduction method had an effect on the results.

Summary: SARS-CoV-2 Omicron quickly spread globally, also in regions with high vaccination coverage, emphasizing the importance of exploring the immunological requirements for protection against Omicron breakthrough infection.The test-negative matched case-control study (N = 964) characterized Omicron breakthrough infections in triple-vaccinated individuals from the ENFORCE cohort. Within 60 days before a PCR test spike-specific IgG levels were significantly lower in cases compared to controls (GMR [95% CI] for BA.2: 0.83 [0.73–0.95], p = 0.006). Multivariable logistic regression showed significant associations between high antibody levels and lower odds of infection (aOR [95% CI] for BA.2 spike-specific IgG: 0.65 [0.48–0.88], p = 0.006 and BA.2 ACE2-blocking antibodies: 0.46 [0.30–0.69], p = 0.0002). A sex-stratified analysis showed more pronounced associations for females than males.High levels of vaccine-induced antibodies provide partial protection against Omicron breakthrough infections. This is important knowledge to further characterize a threshold for protection against new variants and to estimate the necessity and timing of booster vaccination.

Abstract Background Individuals with severe chronic obstructive pulmonary disease (COPD) are often at risk of undernutrition with low health-related quality of life (HRQoL). Undernutrition can worsen COPD and other comorbidities, be an independent predictor of morbidity and functional decline resulting in increased healthcare consumption and increased risk of death. Especially exacerbations and acute infections result in unintentional weight loss. The aim is to investigate the effect of an individualized nutritional intervention among individuals with severe COPD. Methods An open-label randomized controlled trial with two parallel groups. Participants are recruited from the pulmonary outpatient clinic at the Department of Pulmonary and Infectious Diseases, Copenhagen University Hospital, North Zealand, Denmark, and randomly allocated to either the intervention (intervention + standard of care) or control group (standard of care). The intervention has a duration of 3 months and combines individual nutritional care with adherence support and practical tools. It contains 4 elements including an individual nutritional plan, regular contacts, adherence support, and weight diary. The primary outcome is a difference in HRQoL (EQ-5D-5L) between the intervention and control group 3 months after baseline. Difference in functional capacity (grip strength, 30-s stand chair test, and physical activity), disease-specific quality of life (COPD Assessment Test), anxiety and depression (Hospital Anxiety and Depression Scale), nutritional parameters (energy and protein intake), anthropometry (weight, body mass index, waist, hip, and upper arm circumference), body composition (total fat-free and fat mass and indices), and prognosis (exacerbations, oxygen therapy, hospital contacts, and mortality) 3 months after baseline will be included as secondary outcomes. Data will be collected through home visits at baseline and 1 and 3 months after baseline. Discussion Currently, nutritional care is a neglected area of outpatient care among individuals with severe COPD. If this patient-centered approach can demonstrate a positive impact on HRQoL, mortality, and hospital contacts, it should be recommended as part of end-of-life care for individuals with severe COPD. Trial registration ClinicalTrials.gov NCT04873856 . Registered on May 3, 2021.

Abstract Background Viral shedding and neutralizing antibody (NAb) dynamics among patients hospitalized with severe coronavirus disease 2019 (COVID-19) and immune correlates of protection have been key questions throughout the pandemic. We investigated the duration of reverse transcriptase-polymerase chain reaction (RT-PCR) positivity, infectious viral shedding and NAb titers as well as the association between NAb titers and disease severity in hospitalized COVID-19 patients in Denmark 2020–2021. Materials and methods Prospective single-center observational cohort study of 47 hospitalized COVID-19 patients. Oropharyngeal swabs were collected at eight time points during the initial 30 days of inclusion. Serum samples were collected after a median time of 7 (IQR 5 – 10), 37 (IQR 35 – 38), 97 (IQR 95 – 100), and 187 (IQR 185 – 190) days after symptom onset. NAb titers were determined by an in-house live virus microneutralization assay. Viral culturing was performed in Vero E6 cells. Results Patients with high disease severity had higher mean log2 NAb titers at day 37 (1.58, 95% CI [0.34 –2.81]), 97 (2.07, 95% CI [0.53–3.62]) and 187 (2.49, 95% CI [0.20– 4.78]) after symptom onset, compared to patients with low disease severity. Peak viral load (0.072, 95% CI [− 0.627 – 0.728]), expressed as log10 SARS-CoV-2 copies/ml, was not associated with disease severity. Virus cultivation attempts were unsuccessful in almost all (60/61) oropharyngeal samples collected shortly after hospital admission. Conclusions We document an association between high disease severity and high mean NAb titers at days 37, 97 and 187 after symptom onset. However, peak viral load during admission was not associated with disease severity. Trial registration. The study is registered at https://clinicaltrials.gov/ (NCT05274373).

Abstract Background Screening is defined as the identification of unrecognized disease in an apparently healthy population. Symptomatic individuals are recommended to contact a physician instead of participating in screening. However, in colorectal cancer (CRC) screening this approach may be problematic as abdominal symptoms are nonspecific. This study aimed at identifying the prevalence of self-reported abdominal symptoms among screening-eligible men and women aged 50–74 years. Methods This cross-sectional survey study included 11,537 individuals aged 50–74 years invited for CRC screening from 9 to 23 September 2019. Descriptive statistics of responders experiencing alarm symptoms of CRC, Low Anterior Resection Syndrome Score (LARS) and the Patient Assessment of Constipation-Symptoms (PAC-SYM) were derived. The association between abdominal symptoms and demographic and socioeconomic variables were estimated by prevalence ratio (PR) using a Poisson regression model with robust variance. Results A total of 5488 respondents were included. The respondents were more likely women, of older age, Danish, cohabiting and had higher education and income level compared to non-respondents. Abdominal pain more than once a week was experienced by 12.0% of the respondents. Of these, 70.8% had been experiencing this symptom for >1 month. Fresh blood in the stool was experienced by 0.7% and of these 82.1% for >1 month. About one third of those experiencing alarm symptoms more than once a week for >1 month had not consulted a doctor. A total of 64.1% of the respondents had no LARS, 21.7% had minor LARS and 14.2% had major LARS. The median PAC-SYM score was 0.33 (Interquartile range (IQR): 0.17;0.75), the median abdominal score was 0.50 (IQR: 0.00;1.00), median rectal score 0.00 (IQR:0.00;0.33) and median stool score 0.40 (IQR: 0.00;0.80). Men and those aged 65–74 reported less symptoms than women and those aged 50–64 years, respectively. Conclusions This study illustrated that abdominal symptoms were frequent among screening-eligible men and women. This should be taken into account when implementing and improving CRC screening strategies. A concerning high number of the respondents experiencing alarm symptoms had not consulted a doctor. This calls for attention to abdominal symptoms in general and how those with abdominal symptoms should participate in CRC screening.

Backwashing rapid sand filters causes inadvertent displacement of filter media grains from their previous depths. This displacement can affect the hydraulic function of filters by mixing or segregating media grains, and the function of biofilters through displacement of active biomass and coatings from proper depths. This study quantifies grain displacement in a pilot-scale filter using tracer grains of colored sand, glass beads, anthracite and garnet to determine the effect of grain size, density and shape on grain displacement. Statistical moments are used to describe the depth distributions resulting from displacement during backwashing. Results show that significant grain displacement occurs during backwash consisting of air scour, air-and-water wash and sub-fluidization water-only wash. Here, displacement is largely independent of grain size, density and shape. When fluidization backwash is used, greater displacement and more dependence on grain characteristics is seen. A variety of grain movement phenomena can be observed during the backwashing steps, indicating that grain movement and therefore the resulting displacement is highly inhomogeneous in four dimensions. These results have direct practical implications for the design of rapid sand filters and the optimization of backwashing procedures, while suggesting that the current widespread backwashing practice used in the case study country (Denmark) should be abandoned.

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated disease coronavirus disease 2019 (COVID-19), is a worldwide emergency. Demographic, comorbidity and laboratory determinants of death and of ICU admission were explored in all Danish hospitalised patients. Methods National health registries were used to identify all hospitalized patients with a COVID-19 diagnosis. We obtained demographics, Charlson Comorbidity Index (CCI), and laboratory results on admission and explored prognostic factors for death using multivariate Cox proportional hazard regression and competing risk survival analysis. Results Among 2431 hospitalised patients with COVID-19 between February 27 and July 8 (median age 69 years [IQR 53–80], 54.1% males), 359 (14.8%) needed admission to an intensive care unit (ICU) and 455 (18.7%) died within 30 days of follow-up. The seven-day cumulative incidence of ICU admission was lower for females (7.9%) than for males (16.7%), (p

BackgroundChildren born to parents with severe mental illness are at increased risk of mental and behavioral difficulties during childhood. We aimed to investigate the occurrence of clinically significant behavioral difficulties in 7-year-old children of parents diagnosed with schizophrenia or bipolar disorder as well as in control children by using the Strengths and Difficulties Questionnaire (SDQ). Further, we aimed to determine if the SDQ could function as a screening instrument for clinically relevant behavioral problems of children at high risk of these severe mental illnesses.MethodsBy means of the Danish National Registers, we established a cohort of 522 7-year old children stratified by familial high risk for schizophrenia spectrum disorder (N = 202), bipolar disorder (N =120), and controls (N = 200). The child's primary caregiver completed the SDQ parent version and the Child Behavior Checklist (CBCL) while the schoolteacher completed the SDQ teacher version and the CBCL teacher equivalent; the Teachers Report Form (TRF). Finally, global functioning was assessed with the Children's Global Assessment Scale (CGAS).ResultsChildren with familial high risk of schizophrenia spectrum disorder or bipolar disorder have a significantly increased risk (OR = 3.8 and 2.3) of suffering clinically significant behavioral difficulties at age 7-years according to SDQ parent ratings. The SDQ discriminates with moderate to high sensitivity and high specificity between familial high-risk children with and without a psychiatric diagnosis and has overall compelling discriminatory abilities in line with the more time consuming CBCL/TRF.Conclusions Familial high-risk children have more behavioral difficulties and more frequently at a level indicative of mental illness compared to control children as measured by the SDQ. The SDQ works well as a screening instrument for clinically relevant behavioral problems in high-risk children.

Monitoring specific underlying causes of death in solid organ transplant (SOT) recipients is important in order to identify emerging trends and health challenges. This retrospective cohort study includes all SOT recipients transplanted at Rigshospitalet between January 1st, 2010 and December 31st, 2019. The underlying cause of death was determined using the newly developed Classification of Death Causes after Transplantation (CLASS) method. Cox regression analyses assessed risk factors for all-cause and cause-specific mortality. Of the 1774 SOT recipients included, 299 patients died during a total of 7511 person-years of follow-up (PYFU) with cancer (N = 57, 19%), graft rejection (N = 55, 18%) and infections (N = 52, 17%) being the most frequent causes of death. We observed a lower risk of all-cause death with increasing transplant calendar year (HR 0.91, 95% CI 0.86–0.96 per 1-year increase), alongside death from graft rejection (HR 0.84 per year, 95% CI 0.74–0.95) and death from infections (HR 0.86 per year, 95% CI 0.77–0.97). Further, there was a trend towards lower cumulative incidence of death from cardiovascular disease, graft failure and cancer in more recent years, while death from other organ specific and non-organ specific causes did not decrease. All-cause mortality among SOT recipients has decreased over the past decade, mainly due to a decrease in graft rejection- and infection-related deaths. Conversely, deaths from a broad range of other causes have remained unchanged, suggesting that cause of death among SOT recipients is increasingly diverse and warrants a multidisciplinary effort and attention in the future.

Monitoring specific underlying causes of death in solid organ transplant (SOT) recipients is important in order to identify emerging trends and health challenges. This retrospective cohort study includes all SOT recipients transplanted at Rigshospitalet between January 1st, 2010 and December 31st, 2019. The underlying cause of death was determined using the newly developed Classification of Death Causes after Transplantation (CLASS) method. Cox regression analyses assessed risk factors for all-cause and cause-specific mortality. Of the 1774 SOT recipients included, 299 patients died during a total of 7511 person-years of follow-up (PYFU) with cancer (N = 57, 19%), graft rejection (N = 55, 18%) and infections (N = 52, 17%) being the most frequent causes of death. We observed a lower risk of all-cause death with increasing transplant calendar year (HR 0.91, 95% CI 0.86-0.96 per 1-year increase), alongside death from graft rejection (HR 0.84 per year, 95% CI 0.74-0.95) and death from infections (HR 0.86 per year, 95% CI 0.77-0.97). Further, there was a trend towards lower cumulative incidence of death from cardiovascular disease, graft failure and cancer in more recent years, while death from other organ specific and non-organ specific causes did not decrease. All-cause mortality among SOT recipients has decreased over the past decade, mainly due to a decrease in graft rejection- and infection-related deaths. Conversely, deaths from a broad range of other causes have remained unchanged, suggesting that cause of death among SOT recipients is increasingly diverse and warrants a multidisciplinary effort and attention in the future.

Summary: Background: Patients with active acromegaly exhibit insulin resistance despite a lean phenotype whereas controlled disease improves insulin sensitivity and increases fat mass. The mechanisms underlying this paradox remain elusive, but growth hormone (GH)-induced lipolysis plays a central role. The aim of the study was to investigative the molecular mechanisms of insulin resistance dissociated from obesity in patients with acromegaly. Methods: In a prospective study, twenty-one patients with newly diagnosed acromegaly were studied at diagnosis and after disease control obtained by either surgery alone (n=10) or somatostatin analogue (SA) treatment (n=11) with assessment of body composition (DXA scan), whole body and tissue-specific insulin sensitivity and GH and insulin signalling in adipose tissue and skeletal muscle. Findings: Disease control of acromegaly significantly reduced lean body mass (p

Objective: Growth hormone (GH) stimulates lipolysis, but the underlying mechanisms remain incompletely understood. We examined the effect of GH on the expression of lipolytic regulators in adipose tissue (AT). Methods: In a randomized, placebo-controlled, cross-over study, nine men were examined after injection of 1) a GH bolus and 2) a GH-receptor antagonist (pegvisomant) followed by four AT biopsies. In a second study, eight men were examined in a 2 × 2 factorial design including GH infusion and 36-h fasting with AT biopsies obtained during a basal period and a hyperinsulinemic-euglycemic clamp. Expression of GH-signaling intermediates and lipolytic regulators were studied by PCR and western blotting. In addition, mechanistic experiments in mouse models and 3T3-L1 adipocytes were performed. Results: The GH bolus increased circulating free fatty acids (p

Activation of skeletal muscle contractions require that action potentials can be excited and propagated along the muscle fibers. Recent studies have revealed that muscle fiber excitability is regulated during repeated firing of action potentials by cellular signaling systems that control the function of ion channel that determine the resting membrane conductance (Gm). In fast-twitch muscle, prolonged firing of action potentials triggers a marked increase in Gm, reducing muscle fiber excitability and causing action potential failure. Both ClC-1 and KATP ion channels contribute to this Gm rise, but the exact molecular regulation underlying their activation remains unclear. Studies in expression systems have revealed that ClC-1 is able to bind adenosine nucleotides, and that low adenosine nucleotide levels result in ClC-1 activation. In three series of experiments, this study aimed to explore whether ClC-1 is also regulated by adenosine nucleotides in native skeletal muscle fibers, and whether the adenosine nucleotide sensitivity of ClC-1 could explain the rise in Gm muscle fibers during prolonged action potential firing. First, whole cell patch clamping of mouse muscle fibers demonstrated that ClC-1 activation shifted in the hyperpolarized direction when clamping pipette solution contained 0 mM ATP compared with 5 mM ATP. Second, three-electrode Gm measurement during muscle fiber stimulation showed that glycolysis inhibition, with 2-deoxy-glucose or iodoacetate, resulted in an accelerated and rapid >400% Gm rise during short periods of repeated action potential firing in both fast-twitch and slow-twitch rat, and in human muscle fibers. Moreover, ClC-1 inhibition with 9-anthracenecarboxylic acid resulted in either an absence or blunted Gm rise during action potential firing in human muscle fibers. Third, Gm measurement during repeated action potential firing in muscle fibers from a murine McArdle disease model suggest that the rise in Gm was accelerated in a subset of fibers. Together, these results are compatible with ClC-1 function being regulated by the level of adenosine nucleotides in native tissue, and that the channel operates as a sensor of skeletal muscle metabolic state, limiting muscle excitability when energy status is low.

The genetic architecture of the small and isolated Greenlandic population is advantageous for identification of novel genetic variants associated with cardio-metabolic traits. We aimed to identify genetic loci associated with body mass index (BMI), to expand the knowledge of the genetic and biological mechanisms underlying obesity. Stage 1 BMI-association analyses were performed in 4,626 Greenlanders. Stage 2 replication and meta-analysis were performed in additional cohorts comprising 1,058 Yup'ik Alaska Native people, and 1,529 Greenlanders. Obesity-related traits were assessed in the stage 1 study population. We identified a common variant on chromosome 11, rs4936356, where the derived G-allele had a frequency of 24% in the stage 1 study population. The derived allele was genome-wide significantly associated with lower BMI (beta (SE), -0.14 SD (0.03), p = 3.2x10-8), corresponding to 0.64 kg/m2 lower BMI per G allele in the stage 1 study population. We observed a similar effect in the Yup'ik cohort (-0.09 SD, p = 0.038), and a non-significant effect in the same direction in the independent Greenlandic stage 2 cohort (-0.03 SD, p = 0.514). The association remained genome-wide significant in meta-analysis of the Arctic cohorts (-0.10 SD (0.02), p = 4.7x10-8). Moreover, the variant was associated with a leaner body type (weight, -1.68 (0.37) kg; waist circumference, -1.52 (0.33) cm; hip circumference, -0.85 (0.24) cm; lean mass, -0.84 (0.19) kg; fat mass and percent, -1.66 (0.33) kg and -1.39 (0.27) %; visceral adipose tissue, -0.30 (0.07) cm; subcutaneous adipose tissue, -0.16 (0.05) cm, all p

The use of biofilters to produce drinking water from anaerobic groundwater is widespread in some European countries. A major disadvantage of biofilters is the long start-up period required for virgin filter medium to become fully functional. Although individual aspects of biofilter start-up have previously been investigated, no comprehensive study in full scale using inherent inoculation has previously been documented. A thorough investigation of a full-scale drinking water biofilter was carried out over 10 weeks of start-up. The many spatial and temporal changes taking place during start-up were documented using a holistic approach. In addition to collection of many samples over time (frequency) and space (filter depth), this study entailed the use of multiple sample media (water, backwash water and filter media) and multiple types of analyses (physical, chemical and microbiological). The decrease in filter effluent concentrations of individual substances to compliance levels followed a specific order that was shown to coincide with the spatiotemporal development of bacteria on the filter media. Due to the abiotic nature of the iron removal process, iron disappears at the earliest in the start-up period followed by substances that require growth of microorganisms. Ammonium disappears next, with nitrite appearing briefly near the end of ammonium removal, followed by manganese. The thorough overall picture obtained by these efforts provides guidance for optimization and monitoring of the start-up. Guidance for optimization includes shortening the start-up by focusing on kick-starting the ammonium removal; limiting the monitoring burden (at-line measurements of ammonium in finished water supplemented with manual manganese measurements when ammonium removal is complete); and improving filter design by isolating the removal processes in separate, smaller filters.

This review aims to clarify the relation between the ratio of omega-6 to omega-3 fatty acids and the development of depression. It is explained how these fatty acids are involved in the production of eicosanoids and how these fatty acids can affect the membrane fluidity, by their incorporation into membrane phospholipids. In addition, it is described how omega-3 derivatives are shown to regulate gene transcription. In view of the pathophysiology of depression, the mechanisms of how an altered ratio of omega-6 to omega-3 could be involved in depression are discussed. Possible mechanisms could include an increased production of pro-inflammatory cytokines, which can activate the HPA axis and a changed membrane fluidity, which potentially affects membrane bound enzymes, ion channels, receptor activity and neurotransmitter binding. In view of clinical trials, it is also discussed whether omega-3 supplementation could have a beneficial effect in the treatment of depressive patient. There are strong indications that an increased ratio of membrane omega-6 to omega-3 is involved in the pathogenesis of depression and so far, omega-3 supplementation has shown positive effects in clinical trials.

Despite promising anti-cancer properties in vitro, all titanium-based pharmaceuticals have failed in vivo. Likewise, no target-specific positron emission tomography (PET) tracer based on the radionuclide 45Ti has been developed, notwithstanding its excellent PET imaging properties. In this contribution, we present liquid−liquid extraction (LLE) in flow-based recovery and the purification of 45Ti, computer-aided design, and the synthesis of a salan-natTi/45Ti-chelidamic acid (CA)-prostate-specific membrane antigen (PSMA) ligand containing the Glu-urea-Lys pharmacophore. The compound showed compromised serum stability, however, no visible PET signal from the PC3+ tumor was seen, while the ex vivo biodistribution measured the tumor accumulation at 1.1% ID/g. The in vivo instability was rationalized in terms of competitive citrate binding followed by Fe(III) transchelation. The strategy to improve the in vivo stability by implementing a unimolecular ligand design is presented.

Background: Tuberculosis continues to disproportionately affect many Indigenous populations in the USA, Canada, and Greenland. We aimed to investigate whether population-based tuberculosis-specific interventions or changes in general health and socioeconomic indicators, or a combination of these factors, were associated with changes in tuberculosis incidence in these Indigenous populations. Methods: For this population-based study we examined annual tuberculosis notification rates between 1960 and 2014 in six Indigenous populations of the USA, Canada, and Greenland (Inuit [Greenland], American Indian and Alaska Native [Alaska, USA], First Nations [Alberta, Canada], Cree of Eeyou Istchee [Quebec, Canada], Inuit of Nunavik [Quebec, Canada], and Inuit of Nunavut [Canada]), as well as the general population of Canada. We used mixed-model linear regression to estimate the association of these rates with population-wide interventions of bacillus Calmette-Guérin (BCG) vaccination of infants, radiographic screening, or testing and treatment for latent tuberculosis infection (LTBI), and with other health and socioeconomic indicators including life expectancy, infant mortality, diabetes, obesity, smoking, alcohol use, crowded housing, employment, education, and health expenditures. Findings: Tuberculosis notification rates declined rapidly in all six Indigenous populations between 1960 and 1980, with continued decline in Indigenous populations in Alberta, Alaska, and Eeyou Istchee thereafter but recrudescence in Inuit populations of Nunavut, Nunavik, and Greenland. Annual percentage reductions in tuberculosis incidence were significantly associated with two tuberculosis control interventions, relative to no intervention, and after adjustment for infant mortality and smoking: BCG vaccination (–11%, 95% CI −6 to −17) and LTBI screening and treatment (–10%, −3 to −18). Adjusted associations were not significant for chest radiographic screening (–1%, 95% CI −7 to 5). Declining tuberculosis notification rates were significantly associated with increased life expectancy (–37·8 [95% CI −41·7 to −33·9] fewer cases per 100 000 for each 1-year increase) and decreased infant mortality (–9·0 [–9·5 to −8·6] fewer cases per 100 000 for each death averted per 1000 livebirths) in all six Indigenous populations, but no significant associations were observed for other health and socioeconomic indicators examined. Interpretation: Population-based BCG vaccination of infants and LTBI screening and treatment were associated with significant decreases in tuberculosis notification rates in these Indigenous populations. These interventions should be reinforced in populations still affected by tuberculosis, while also addressing the persistent health and socioeconomic disparities. Funding: Public Health Department of the Cree Board of Health and Social Services of James Bay.

BACKGROUND:Indigenous Arctic people suffer from high rates of infectious diseases. However, the burden of central nervous system (CNS) infections is poorly documented. This study aimed to estimate incidence rates and mortality of CNS infections among Inuits and non-Inuits in Greenland and in Denmark. METHODS:We conducted a nationwide cohort study using the populations of Greenland and Denmark 1990-2012. Information on CNS infection hospitalizations and pathogens was retrieved from national registries and laboratories. Incidence rates were estimated as cases per 100,000 person-years. Incidence rate ratios were calculated using log-linear Poisson-regression. Mortality was estimated using Kaplan-Meier curves and Log Rank test. RESULTS:The incidence rate of CNS infections was twice as high in Greenland (35.6 per 100,000 person years) as in Denmark (17.7 per 100,000 person years), but equally high among Inuits in Greenland and Denmark (38.2 and 35.4, respectively). Mortality from CNS infections was 2 fold higher among Inuits (10.5%) than among non-Inuits (4.8%) with a fivefold higher case fatality rate in Inuit toddlers. CONCLUSION:Overall, Inuits living in Greenland and Denmark suffer from twice the rate of CNS infections compared with non-Inuits, and Inuit toddlers carried the highest risk of mortality. Further studies regarding risk factors such as genetic susceptibility, life style and socioeconomic factors are warranted.

Background: The incidence of tuberculosis (TB) disease in Greenland doubled in the 1990s. To combat the increase, national TB interventions were initiated in 2000 and strengthened in 2007. Objective: To determine whether the effect of interventions could be detected, we estimated the TB disease risk among children≤15 years before and after interventions were implemented. Design: For a study cohort, we recruited all children ≤15 years of age included in the Greenlandic Civil Registration System (CRS) from 1990 to 2010. The CRS identifier was used to link cohort participants with TB cases identified based on the Greenlandic National TB registry. Bacille Calmette Guerin (BCG) vaccination status was identified through year of birth, as BCG was offered to newborns born either before 1991 or after 1996. Years with interventions were defined as 2000–2006 (primary interventions) and 2007–2010 (intensified interventions). Risk of TB was estimated using Poisson regression. Results: The study included 35,858 children, of whom 209 had TB disease. The TB disease incidence decreased after interventions were implemented (2007–2010: IRR [incidence rate ratios] 0.62, 95% CI: 0.39–0.95, p=0.03, compared with the 1995–1999 period). The TB disease risk was inversely associated with BCG vaccination (IRR: 0.54, 95% CI: 0.41–0.72, p

The bacterial community structures in High-Arctic snow over sea ice and an ice-covered freshwater lake were examined by pyrosequencing of 16S rRNA genes and 16S rRNA gene sequencing of cultivated isolates. Both the pyrosequence and cultivation data indicated that the phylogenetic composition of the microbial assemblages was different within the snow layers and between snow and freshwater. The highest diversity was seen in snow. In the middle and top snow layers, Proteobacteria, Bacteroidetes and Cyanobacteria dominated, although Actinobacteria and Firmicutes were relatively abundant also. High numbers of chloroplasts were also observed. In the deepest snow layer, large percentages of Firmicutes and Fusobacteria were seen. In freshwater, Bacteroidetes, Actinobacteria and Verrucomicrobia were the most abundant phyla while relatively few Proteobacteria and Cyanobacteria were present. Possibly, light intensity controlled the distribution of the Cyanobacteria and algae in the snow while carbon and nitrogen fixed by these autotrophs in turn fed the heterotrophic bacteria. In the lake, a probable lower light input relative to snow resulted in low numbers of Cyanobacteria and chloroplasts and, hence, limited input of organic carbon and nitrogen to the heterotrophic bacteria. Thus, differences in the physicochemical conditions may play an important role in the processes leading to distinctive bacterial community structures in High-Arctic snow and freshwater.

The occurrence and distribution of clinically relevant bacterial virulence genes across natural (non-human) environments is not well understood. We aimed to investigate the occurrence of homologues to bacterial human virulence genes in a variety of ecological niches to better understand the role of natural environments in the evolution of bacterial virulence. Twentyfour bacterial virulence genes were analyzed in 47 diverse environmental metagenomic datasets, representing various soils, seawater, freshwater, marine sediments, hot springs, the deep-sea, hypersaline mats, microbialites, gutless worms and glacial ice. Homologues to 17 bacterial human virulence genes, involved in urinary tract infections, gastrointestinal diseases, skin diseases, and wound and systemic infections, showed global ubiquity. A principal component analysis did not demonstrate clear trends across the metagenomes with respect to occurrence and frequency of observed gene homologues. Full-length (>95%) homologues of several virulence genes were identified, and translated sequences of the environmental and clinical genes were up to 50-100% identical. Furthermore, phylogenetic analyses indicated deep branching positions of some of the environmental gene homologues, suggesting that they represent ancient lineages in the phylogeny of the clinical genes. Fifteen virulence gene homologues were detected in metagenomes based on metatranscriptomic data, providing evidence of environmental expression. The ubiquitous presence and transcription of the virulence gene homologues in non-human environments point to an important ecological role of the genes for the activity and survival of environmental bacteria. Furthermore, the high degree of sequence conservation between several of the environmental and clinical genes suggests common ancestral origins.

OBJECTIVE: To examine the risk factors for Mycobacterium tuberculosis infection (MTI) among Greenlandic children for the purpose of identifying those at highest risk of infection. METHODS: Between 2005 and 2007, 1797 Greenlandic schoolchildren in five different areas were tested for MTI with an interferon gamma release assay (IGRA) and a tuberculin skin test (TST). Parents or guardians were surveyed using a standardized self-administered questionnaire to obtain data on crowding in the household, parents' educational level and the child's health status. Demographic data for each child - i.e. parents' place of birth, number of siblings, distance between siblings (next younger and next older), birth order and mother's age when the child was born - were also extracted from a public registry. Logistic regression was used to check for associations between these variables and MTI, and all results were expressed as odds ratios (ORs) and 95% confidence intervals (CIs). Children were considered to have MTI if they tested positive on both the IGRA assay and the TST. FINDINGS: The overall prevalence of MTI was 8.5% (152/1797). MTI was diagnosed in 26.7% of the children with a known TB contact, as opposed to 6.4% of the children without such contact. Overall, the MTI rate was higher among Inuit children (OR:4.22; 95% CI: 1.55-11.5) and among children born less than one year after the birth of the next older sibling (OR:2.48; 95% CI: 1.33-4.63). Self-reported TB contact modified the profile to include household crowding and low mother's education. Children who had an older MTI-positive sibling were much more likely to test positive for MTI themselves (OR:14.2; 95% CI: 5.75-35.0) than children without an infected older sibling. CONCLUSION: Ethnicity, sibling relations, number of household residents and maternal level of education are factors associated with the risk of TB infection among children in Greenland. The strong household clustering of MTI suggests that family sources of exposure are important.

This article discusses some alternative or critical theoretical contributions regarding globalization and labor. The main question in this discussion is if there are changes in direction of a possible revitalization of labor movements and if international solidarity can increase due to globalization. This question also relates to discussions of changes in division of work, the concept of work, working class, commodification, decommodification, and new centers of global production—all related to different paradigms or new concepts. The reason or need for reconceptualizing comes from the great transformation of capitalism in forms of neoliberal globalization, in a different direction than predicted by Polanyi. That is, instead of increased public sector decommodification (not profit- or market-oriented production) and national regulation, embedding capitalist markets, as seen after 1945, the last three decades have witnessed a countertransformation and large-scale recommodification by privatizing, disembedding, and deregulating global markets. As a consequence, inequality in income and working life conditions has increased in most countries and been used to press trade unions. Western industrial unions have been declining as many industries and labor-intensive, low-paid jobs moved to developing countries. Most blue-collar jobs are now in Asia, especially China, with about one-third of its employment blue collars. Is the center of global capital-labor contradictions and dynamics moving to the South, with a possibility of a new revitalization of labor and international solidarity? We discuss different optimistic and pessimistic views on a possible international revitalization of labor.