Environmental drivers of increased ecosystem respiration in a warming tundra.

Arctic and alpine tundra ecosystems are large reservoirs of organic carbon1,2. Climate warming may stimulate ecosystem respiration and release carbon into the atmosphere3,4. The magnitude and persistency of this stimulation and the environmental mechanisms that drive its variation remain uncertain5-7. This hampers the accuracy of global land carbon-climate feedback projections7,8. Here we synthesize 136 datasets from 56 open-top chamber in situ warming experiments located at 28 arctic and alpine tundra sites which have been running for less than 1 year up to 25 years. We show that a mean rise of 1.4 °C [confidence interval (CI) 0.9-2.0 °C] in air and 0.4 °C [CI 0.2-0.7 °C] in soil temperature results in an increase in growing season ecosystem respiration by 30% [CI 22-38%] (n = 136). Our findings indicate that the stimulation of ecosystem respiration was due to increases in both plant-related and microbial respiration (n = 9) and continued for at least 25 years (n = 136). The magnitude of the warming effects on respiration was driven by variation in warming-induced changes in local soil conditions, that is, changes in total nitrogen concentration and pH and by context-dependent spatial variation in these conditions, in particular total nitrogen concentration and the carbon:nitrogen ratio. Tundra sites with stronger nitrogen limitations and sites in which warming had stimulated plant and microbial nutrient turnover seemed particularly sensitive in their respiration response to warming. The results highlight the importance of local soil conditions and warming-induced changes therein for future climatic impacts on respiration.

Supramolecular Coordination Cages for Artificial Photosynthesis and Synthetic Photocatalysis.

Because sunlight is the most abundant energy source on earth, it has huge potential for practical applications ranging from sustainable energy supply to light driven chemistry. From a chemical perspective, excited states generated by light make thermodynamically uphill reactions possible, which forms the basis for energy storage into fuels. In addition, with light, open-shell species can be generated which open up new reaction pathways in organic synthesis. Crucial are photosensitizers, which absorb light and transfer energy to substrates by various mechanisms, processes that highly depend on the distance between the molecules involved. Supramolecular coordination cages are well studied and synthetically accessible reaction vessels with single cavities for guest binding, ensuring close proximity of different components. Due to high modularity of their size, shape, and the nature of metal centers and ligands, cages are ideal platforms to exploit preorganization in photocatalysis. Herein we focus on the application of supramolecular cages for photocatalysis in artificial photosynthesis and in organic photo(redox) catalysis. Finally, a brief overview of immobilization strategies for supramolecular cages provides tools for implementing cages into devices. This review provides inspiration for future design of photocatalytic supramolecular host-guest systems and their application in producing solar fuels and complex organic molecules.

National Trends in Inpatient Hospital Outcomes of Children with Osteogenesis Imperfecta and the Importance of Extra-skeletal Manifestations: A Kids' Inpatient Database Study.

OBJECTIVE: To investigate the extent of extra-skeletal manifestations along with inpatient outcomes and complications associated with osteogenesis imperfecta (OI). STUDY DESIGN: This cross-sectional study utilized the Kids' Inpatient Database (KID) as part of the Healthcare Cost and Utilization Project (HCUP) to investigate inpatient hospital outcomes and management in patients with OI from 1997 through 2016. Data regarding hospital characteristics, cost of treatment, inpatient outcomes, and procedures were collected and analyzed. RESULTS: There were 7,291 admissions that listed OI as a diagnosis in the KID database from 1997 through 2016. Unexpectedly, over one third of all admissions in these children with OI presented with an extra-skeletal manifestation. The rate of major complications was 3.85%. The rate of minor complications was 19.4%, most commonly respiratory problems. Mortality rate was 18.2 % in the neonatal period and 1.0% in all other admissions. Total charges of hospital stay increased over the years. CONCLUSION: We identified a striking prevalence of extra-skeletal manifestations in OI along with inpatient outcomes and complications associated with OI, of which respiratory complications were predominant. We observed a significant financial burden for patients with OI and identified additional risks for financial crisis, in addition to disparities in care identified among socioeconomic groups. These data contribute to a more holistic understanding of OI from diagnosis to management.

Bicaudal D2 autoantibodies are highly specific for systemic sclerosis.

OBJECTIVE: Autoantibodies directed against the intracellular protein bicaudal D2 (BICD2) have been identified as a specific marker of systemic sclerosis (SSc). Since autoantibodies are of value in predicting disease onset and identifying meaningful clinical subsets, as well as having prognostic value, this study aimed to establish the prevalence of BICD2 autoantibodies (anti-BICD2) in a cohort of patients with connective tissue disease and healthy controls. METHOD: In this cross-sectional study, 363 patients with connective tissue disease (121 SSc, 141 systemic lupus erythematosus, 101 myositis, and 100 blood donors) were tested for the presence of anti-BICD2. All SSc patients were tested for specific anti-nuclear antibodies (ANAs), and clinical and laboratory associations were evaluated in the SSc patients, stratified by anti-BICD2 status. RESULTS: In the SSc cohort, 35 patients had autoantibodies directed against BICD2. The specificity of anti-BICD2 in SSc patients was 96.5%; however, the sensitivity was only 28.9%. Anti-BICD2 and centromere autoantibodies were present together in 91% of the anti-BICD2-positive SSc patients, and in none of the cases was anti-BICD2 the only antibody present. Anti-BICD2-positive patients had lower forced expiratory volume in 1 s (FEV1) (p = 0.01) and lower carbon monoxide transfer coefficient (KCO) (p = 0.01) than anti-BICD2-negative SSc patients, but they had higher forced vital capacity (p = 0.03). CONCLUSION: Autoantibodies against BICD2 were highly specific for SSc patients. Reduced FEV1 and KCO in anti-BICD2-positive patients may indicate that the presence of anti-BICD2 is associated with altered lung function in an unknown pathophysiological manner, which awaits further elucidation.

Occupational risk of COVID-19 in foreign-born employees in Denmark.

BACKGROUND: Foreign-born workers in high-income countries experience higher rates of COVID-19 but the causes are only partially known. AIMS: To examine if the occupational risk of COVID-19 in foreign-born workers deviates from the risk in native-born employees in Denmark. METHODS: Within a registry-based cohort of all residents employed in Denmark (n = 2 451 542), we identified four-digit DISCO-08 occupations associated with an increased incidence of COVID-19-related hospital admission during 2020-21 (at-risk occupations). The sex-specific prevalence of at-risk employment in foreign born was compared with the prevalence in native born. Moreover, we examined if the country of birth modified the risk of a positive SARS-CoV-2 polymerase chain reaction (PCR) test and COVID-19-related hospital admission in at-risk occupations. RESULTS: Workers born in low-income countries and male workers from Eastern Europe more often worked in at-risk occupations (relative risks between 1.16 [95% confidence interval {CI} 1.14-1.17] and 1.87 [95% CI 1.82-1.90]). Being foreign-born modified the adjusted risk of PCR test positivity (test for interaction P < 0.0001), primarily because of higher risk in at-risk occupations among men born in Eastern European countries (incidence rate ratio [IRR] 2.39 [95% CI 2.09-2.72] versus IRR 1.19 [95% CI 1.14-1.23] in native-born men). For COVID-19-related hospital admission, no overall interaction was seen, and in women, country of birth did not consistently modify the occupational risk. CONCLUSIONS: Workplace viral transmission may contribute to an excess risk of COVID-19 in male workers born in Eastern Europe, but most foreign-born employees in at-risk occupations seem not to be at higher occupational risk than native born.

Probing the influence of substrate binding on photocatalytic dehalogenation with a heteroleptic supramolecular [M4La2Lb2] square containing PDI photosensitizers as ligands.

Photoredox catalysis is a valuable tool in a large variety of chemical reactions. Main challenges still to be overcome are photodegradation of photocatalysts and substrates, short lifetimes of reactive intermediates, and selectivity issues due to unwanted side reactions. A potential solution to these challenges is the pre-organization of the photosensitizer, substrate and (co)-catalyst in supramolecular self-assembled structures. In such architectures, (organic) dyes can be stabilized, and higher selectivity could potentially be achieved through pre-organizing desired reaction partners via non-covalent interactions. Perylene diimide (PDI) is an organic dye, which can be readily reduced to its mono- and dianion. Excitation of both anions leads to highly reducing excited states, which are able to reduce a variety of substrates via single electron transfer. The incorporation of PDI into a heteroleptic [M4La2Lb2] supramolecular square has been recently demonstrated. Herein we investigate its photophysical properties and demonstrate that incorporated PDI indeed features photocatalytic activity. Initial results suggest that the pre-organisation by binding positively affects the outcome.

Suitability of machine learning models for prediction of clinically defined Stage III/IV periodontitis from questionnaires and demographic data in Danish cohorts.

AIM: To evaluate if, and to what extent, machine learning models can capture clinically defined Stage III/IV periodontitis from self-report questionnaires and demographic data. MATERIALS AND METHODS: Self-reported measures of periodontitis, demographic data and clinically established Stage III/IV periodontitis status were extracted from two Danish population-based cohorts (The Copenhagen Aging and Midlife Biobank [CAMB] and The Danish Health Examination Survey [DANHES]) and used to develop cross-validated machine learning models for the prediction of clinically established Stage III/IV periodontitis. Models were trained using 10-fold cross-validations repeated three times on the CAMB dataset (n = 1476), and the resulting models were validated in the DANHES dataset (n = 3585). RESULTS: The prevalence of Stage III/IV periodontitis was 23.2% (n = 342) in the CAMB dataset and 9.3% (n = 335) in the DANHES dataset. For the prediction of clinically established Stage III/IV periodontitis in the CAMB cohort, models reached area under the receiver operating characteristics (AUROCs) of 0.67-0.69, sensitivities of 0.58-0.64 and specificities of 0.71-0.80. In the DANHES cohort, models derived from the CAMB cohort achieved AUROCs of 0.64-0.70, sensitivities of 0.44-0.63 and specificities of 0.75-0.84. CONCLUSIONS: Applying cross-validated machine learning algorithms to demographic data and self-reported measures of periodontitis resulted in models with modest capabilities for the prediction of Stage III/IV periodontitis in two Danish cohorts.

Cardiac rehabilitation: pedagogical education strategies have positive effect on long-term patient-reported outcomes.

This study examined whether patients attending cardiac rehabilitation (CR) based on the pedagogical strategy learning and coping (LC) led to improved health-related quality of life (HRQL), reduced symptoms of anxiety and depression and improved self-management 6 and 12 months after the completion of CR compared with patients attending CR based on the pedagogical strategy 'Empowerment, Motivation and Medical Adherence' (EMMA). A pragmatic cluster-controlled trial of two pedagogical strategies, LC and EMMA, including 10 primary health care settings and 555 patients diagnosed with ischaemic heart disease and referred to CR between August 2018 and July 2019 was conducted. In total, 312 patients replied to the questionnaires collected at baseline, 12 weeks, 6 months and 12 months after completing CR. Linear regression analyses adjusted for potential confounder variables and cluster effects were performed. We found clinically relevant and statistically significant improvements in HRQL, anxiety, depression and self-management after completing CR. The improvements were sustained at 6 and 12 months after the completion of CR. We found no differences between the two evidence-based patient education strategies. In conclusion, this study supports the use of evidence-based patient education strategies, but there is no evidence to suggest that one pedagogical strategy is superior to the other.

Microvesicles in active lupus nephritis show Toll-like receptor 9-dependent co-expression of galectin-3 binding protein and double-stranded DNA.

Circulating microvesicles (MVs) from patients with systemic lupus erythematosus (SLE) express the type 1 interferon (IFN)-inducible protein galectin-3 binding protein (G3BP), which may enhance their deposition in the glomerular basement membrane. The release of G3BP-expressing MVs from normal peripheral blood mononuclear cells (PBMCs) is induced by Toll-like receptor 9 (TLR-9) ligands, and these vesicles contain autoantibody-accessible double-stranded DNA (dsDNA). This study compares the release of MVs expressing G3BP and dsDNA from PBMCs derived from SLE patients with or without active lupus nephritis (LN) and from healthy donors, and taps further into the potential dependency on IFN-α for their generation and impacts of TLR-7/TLR-9 co-stimulation. PBMCs from 10 healthy donors and 12 SLE patients, six of whom had active LN at study inclusion, were stimulated in-vitro with recombinant human IFN-α and the TLR-9 agonists oligodeoxynucleotide (ODN)2216 or ODN2395 alone or in combination with the TLR-7 agonist gardiquimod. MVs in the supernatants were subsequently isolated by differential centrifugation and their expression of G3BP and dsDNA was quantified by flow cytometry. Stimulation with ODN2395 significantly increased the release of MVs co-expressing G3BP and dsDNA from PBMCs isolated from healthy donors and SLE patients. The expression of G3BP on individual MVs and the proportion of G3BP and dsDNA double-positive MVs released were increased in active LN patients. Neither co-stimulation with gardiquimod nor with the IFN-α inhibitor IN-1 had any effect on the MV release induced by ODN2395. In conclusion, the TLR-9-mediated inducibility of MVs co-expressing G3BP and dsDNA is increased in SLE patients with active LN.

Fragility fractures and health-related quality of life: does socio-economic status widen the gap? A population-based study.

Studying 12,839 fracture cases and 91,426 controls, we found that fractures of the spine and hip are associated with clinically important HRQoL deficits up to 5 years post-fracture. Fracture cases with a low educational attainment are more likely to report very low HRQoL due to a low pre-fracture HRQoL. INTRODUCTION: The aim of this study was to explore the short-term and long-term impact of fractures on health-related quality of life (HRQoL) and to study the effect of educational attainment as a proxy for socio-economic status (SES) on post-fracture HRQoL. METHODS: In a population-based survey including 12,839 fracture cases and 91,426 controls, HRQoL was measured using the physical component score (PCS) and the mental component score (MCS) of the 12-Item Short Form Health Survey (SF-12). Information about fractures, age, sex, ethnicity, comorbidity and SES was obtained from national registers. Multiple regression analysis was conducted to measure the mean HRQoL difference, termed deficit, between non-fracture controls and fracture cases (all fractures combined and fractures at six different skeletal sites). RESULTS: PCS and MCS were significantly lower among fracture cases than among controls. Statistically and clinically important PCS deficits (≥ 5 points) were observed among people with fractures of the spine and hip up to 5 years post-fracture and among people with upper arm fractures up to 1 year post-fracture. Greater deficits were observed for MCS but not for PCS in post-fracture HRQoL in the low than in the high SES group. CONCLUSION: Fractures of the spine and hip are associated with clinically important deficits in physical HRQoL up to 5 years post-fracture. Low educational attainment widened the gap in mental but not in physical post-fracture HRQoL. However, due to low pre-fracture PCS and MCS, people with a low educational attainment and fractures were more likely to report very low HRQoL post-fracture.

Socio-economic inequalities in fragility fracture incidence: a systematic review and meta-analysis of 61 observational studies.

Individuals with low socio-economic status (SES) have a more than 25% higher risk of fragility fractures than individuals with high SES. Body mass index and lifestyle appear to mediate the effect of SES on fracture risk. Strategies to prevent fractures should aim to reduce unhealthy behaviours through tackling structural inequalities. INTRODUCTION: This systematic review and meta-analysis aimed to evaluate the impact of socio-economic status (SES) on fragility fracture risk. METHODS: Medline, Embase, and CINAHL databases were searched from inception to 28 April 2021 for studies reporting an association between SES and fragility fracture risk among individuals aged ≥50 years. Risk ratios (RR) were combined in meta-analyses using random restricted maximum likelihood models, for individual-based (education, income, occupation, cohabitation) and area-based (Index of Multiple Deprivation, area income) SES measures. RESULTS: A total of 61 studies from 26 different countries including more than 19 million individuals were included. Individual-based low SES was associated with an increased risk of fragility fracture (RR 1.27 [95% CI 1.12, 1.44]), whilst no clear association was seen when area-based measures were used (RR 1.08 [0.91, 1.30]). The strength of associations was influenced by the type and number of covariates included in statistical models: RR 2.69 [1.60, 4.53] for individual-based studies adjusting for age, sex and BMI, compared with RR 1.06 [0.92, 1.22] when also adjusted for health behaviours (smoking, alcohol, and physical activity). Overall, the quality of the evidence was moderate. CONCLUSION: Our results show that low SES, measured at the individual level, is a risk factor for fragility fracture. Low BMI and unhealthy behaviours are important mediators of the effect of SES on fracture risk. Strategies to prevent fractures and reduce unhealthy behaviours should aim to tackle structural inequalities in society thereby reducing health inequalities in fragility fracture incidence.

Short- and long-term effects of the patient education strategy-learning and coping-in cardiac rehabilitation: a randomized controlled trial (LC-REHAB).

The objectives were to assess the short- and long-term effect of the patient education strategy 'Learning and Coping' (LC) in cardiac rehabilitation (CR) on health-related quality of life, patient education impact, cardiac risk factors and lifestyle. In total, 825 patients hospitalized with ischaemic heart disease or heart failure were randomized to either LC-CR or standard CR at three Danish hospitals. Teaching approach in LC-CR was situational, inductive and reflective, with experienced patients as co-educators and supplemental interviews. Teaching approach in standard CR was structured and deductive. Outcomes were assessed immediately after CR, and after 3 months (short term), and after 3 years (long term). Between-arm differences in favour of LC-CR were SF-12 'role emotional' (3.7, 95% CI: 0.6-6.8) and MDI depression score (0.9, 0.1-1.8) immediately after CR, exercise capacity (4 W, 1-9) at 3 months and SF-12 'role physical' (4.6, 0.1-9.0) (long term). Between-arm differences in favour of controls were waist circumference (-1.7 cm, -2.3 to -1.0) immediately after CR and HeiQ domain 'Constructive attitudes and approaches' (0.11, 0.04-0.18), triglycerides (-0.12 mmol/l, -0.21 to -0.02), systolic blood pressure (-3.12 mmHg, -5.66 to -0.58) at 3 months. Adding LC strategies to CR provides inconsistent short-term results but improves 'role physical' long term.

The green tea polyphenol epigallocatechin-3-gallate (EGCG) restores CDKL5-dependent synaptic defects in vitro and in vivo.

CDKL5 deficiency disorder (CDD) is a rare X-linked neurodevelopmental disorder that is characterised by early-onset seizures, intellectual disability, gross motor impairment, and autistic-like features. CDD is caused by mutations in the cyclin-dependent kinase-like 5 (CDKL5) gene that encodes a serine/threonine kinase with a predominant expression in the brain. Loss of CDKL5 causes neurodevelopmental alterations in vitro and in vivo, including defective dendritic arborisation and spine maturation, which most likely underlie the cognitive defects and autistic features present in humans and mice. Here, we show that treatment with epigallatocathechin-3-gallate (EGCG), the major polyphenol of green tea, can restore defects in dendritic and synaptic development of primary Cdkl5 knockout (KO) neurons. Furthermore, defective synaptic maturation in the hippocampi and cortices of adult Cdkl5-KO mice can be rescued through the intraperitoneal administration of EGCG, which is however not sufficient to normalise behavioural CDKL5-dependent deficits. EGCG is a pleiotropic compound with numerous cellular targets, including the dual-specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) that is selectively inhibited by EGCG. DYRK1A controls dendritic development and spine formation and its deregulation has been implicated in neurodevelopmental and degenerative diseases. Treatment with another DYRK1A inhibitor, harmine, was capable of correcting neuronal CDKL5-dependent defects; moreover, DYRK1A levels were upregulated in primary Cdkl5-KO neurons in concomitance with increased phosphorylation of Tau, a well-accepted DYRK1A substrate. Altogether, our results indicate that DYRK1A deregulation may contribute, at least in part, to the neurodevelopmental alterations caused by CDKL5 deficiency.

Updated Global Warming Potentials and Radiative Efficiencies of Halocarbons and Other Weak Atmospheric Absorbers.

Human activity has led to increased atmospheric concentrations of many gases, including halocarbons, and may lead to emissions of many more gases. Many of these gases are, on a per molecule basis, powerful greenhouse gases, although at present-day concentrations their climate effect is in the so-called weak limit (i.e., their effect scales linearly with concentration). We published a comprehensive review of the radiative efficiencies (RE) and global warming potentials (GWP) for around 200 such compounds in 2013 (Hodnebrog et al., 2013, https://doi.org/10.1002/rog.20013). Here we present updated RE and GWP values for compounds where experimental infrared absorption spectra are available. Updated numbers are based on a revised "Pinnock curve", which gives RE as a function of wave number, and now also accounts for stratospheric temperature adjustment (Shine & Myhre, 2020, https://doi.org/10.1029/2019MS001951). Further updates include the implementation of around 500 absorption spectra additional to those in the 2013 review and new atmospheric lifetimes from the literature (mainly from WMO (2019)). In total, values for 60 of the compounds previously assessed are based on additional absorption spectra, and 42 compounds have REs which differ by >10% from our previous assessment. New RE calculations are presented for more than 400 compounds in addition to the previously assessed compounds, and GWP calculations are presented for a total of around 250 compounds. Present-day radiative forcing due to halocarbons and other weak absorbers is 0.38 [0.33-0.43] W m-2, compared to 0.36 [0.32-0.40] W m-2 in IPCC AR5 (Myhre et al., 2013, https://doi.org/10.1017/CBO9781107415324.018), which is about 18% of the current CO2 forcing.

Socio-economic inequalities in fragility fracture outcomes: a systematic review and meta-analysis of prognostic observational studies.

Individuals with low socio-economic status (SES) have a higher risk of dying following hip fracture compared with individuals with high SES. Evidence on social inequalities in non-hip fractures is lacking as well as evidence on the impact of SES on health-related quality of life post fracture. INTRODUCTION: Fragility fractures, especially of the hip, cause substantial excess mortality and impairment in health-related quality of life (HRQoL). This systematic review and meta-analysis aimed to investigate the association between socio-economic status (SES) and post-fracture mortality and HRQoL. METHODS: PubMed, EMBASE and CINAHL databases were searched from inception to the last week of November 2018 for studies reporting an association between SES and post-fracture mortality and/or HRQoL among people aged ≥ 50 years. Risk ratios (RRs) were meta-analyzed using a standard inverse-variance-weighted random effects model. Studies using individual-level and area-based SES measures were analyzed separately. RESULTS: A total of 24 studies from 15 different countries and involving more than one million patients with hip fractures were included. The overall risk of mortality within 1-year post-hip fracture in individuals with low SES was 24% higher than in individuals with high SES (RR 1.24, 95% CI 1.19 to 1.29) for individual-level SES measures, and 14% (RR 1.14, 95% CI 1.09 to 1.19) for area-based SES measures. The quality of the evidence for the outcome mortality was moderate. Using individual SES measures, we estimated the excess HRQoL loss to be 5% (95% CI - 1 to 10%) among hip fracture patients with low SES compared with high SES. CONCLUSIONS: We found a consistently increased risk of post-hip fracture mortality with low SES across SES measures and across countries with different political structures and different health and social care infrastructures. The impact of SES on post-fracture HRQoL remains uncertain due to sparse and low-quality evidence.

Lymphopenia and neutropenia are associated with subsequent incident proteinuria in Danish patients with systemic lupus erythematosus.

Objective: The aim of this study was to investigate whether incident proteinuria in patients with systemic lupus erythematosus (SLE) was preceded by changes in blood lymphocytes and neutrophil counts and/or neutrophil-lymphocyte ratio (NLR).Method: SLE patients with no proteinuria before or at the time of classification were included. Longitudinal data on SLE manifestations, vital status, and SLE-associated medications were collected during clinical visits and chart review. Laboratory data were collected through a nationwide database. Lymphopenia, severe lymphopenia, and neutropenia were defined as values below 0.8 × 109, 0.5 × 109, and 2.0 × 109 cells/L, respectively. High NLR was defined as values above the median. Proteinuria was defined by at least two measurements of elevated urine protein excretion (> 0.5 g/day). Hazard ratios (HRs) were calculated by Cox modelling using time-dependent continuous and binary covariates based on multiple laboratory measurements adjusted for use of immunosuppressants.Results: In total, 260 SLE patients were available for the analysis, of whom 30 (12%) developed incident proteinuria following the diagnosis of SLE. Median follow-up time was 73.5 months. Lymphocyte and neutrophil counts, but not NLR, were associated with incident proteinuria. HRs for incident proteinuria were 2.71 for lymphopenia [95% confidence interval (CI) 1.20-6.11], 4.73 for severe lymphopenia (95% CI 1.93-11.59), and 2.54 for neutropenia (95% CI 1.14-5.65).Conclusion: Lymphopenia and neutropenia predicted the risk of first-time proteinuria independently of immunosuppressants.

Effects of the patient education strategy 'Learning and Coping' in cardiac rehabilitation on readmissions and mortality: a randomized controlled trial (LC-REHAB).

We assessed the effects of the patient education strategy 'Learning and Coping' (LC) in cardiac rehabilitation (CR) on mortality and readmissions by exploring results from the LC-REHAB trial. In all, 825 patients with ischaemic heart disease or heart failure were randomized to the intervention arm (LC-CR) or the control arm (standard CR) at three hospitals in Denmark. LC-CR was situational and inductive, with experienced patients as co-educators supplemented with two individual interviews. Group-based training and education hours were the same in both arms. Outcomes were time to death or readmission, length of stay and absolute number of deaths or readmissions. No between-arm differences were found in time to death, first readmission, or length of stay. Within 30 days after completion of CR, the absolute number of all-cause readmissions was 117 in the LC arm and 146 in the control arm, adjusted odds ratio 78 (95% CI: 0.61-1.01), P = 0.06. This trend diminished over time. Adding LC strategies to standard CR showed a short term but no significant long-term effect on mortality or readmissions. However, the study was not powered to detect differences in mortality and morbidity. Thus, a risk of overseeing a true effect was present.

Peptidylarginine deiminase-4 gene polymorphisms are associated with systemic lupus erythematosus and lupus nephritis.

OBJECTIVE: Peptidylarginine deiminase-4 (PAD4) is highly expressed by neutrophils and essential for citrullination occurring during the formation of neutrophil extracellular traps, which have been implicated in the pathogenesis of systemic lupus erythematosus (SLE) and lupus nephritis (LN). Single-nucleotide polymorphisms (SNPs) in PADI4 influence PAD4 expression and functionality. Here, we investigate whether SNPs in PADI4 influence the risk of SLE or LN. METHOD: Altogether, 234 SLE patients and 484 controls were genotyped for nine PADI4 SNPs known to alter PAD4 functionality and/or expression, or to be associated with other autoimmune diseases, using an in-house multiplex Luminex assay. All analyses were adjusted for age and gender. RESULTS: Heterozygosity for rs1748033, and heterozygosity and homozygosity for rs1635564, were associated with increased occurrence of SLE [odds ratio (OR) 1.55, 95% confidence interval (CI) 1.08-2.23; OR 1.52, 95% CI 1.06-2.19; and OR 2.06, 95% CI 1.08-3.93, respectively]. Homozygosity for rs1635564 was also associated with increased occurrence of LN (OR 3.35, 95% CI 1.2-10.97). Notably, gene dose effects of the rs1635564 variant allele were observed for SLE (p = 0.005) and LN (p = 0.01). Carriage of minor alleles of five other SNPs (rs11203366, rs11203367, rs874881, rs2240340, and rs11203368) was associated with increased occurrence of LN and hypertension. CONCLUSION: The rs1635564 polymorphism of PADI4 is a candidate risk factor for SLE, particularly with renal involvement. Additional PADI4 polymorphisms also conferred increased risk of LN. Overall, these findings support the notion of PAD4 contributing to the pathogenesis of SLE and LN.

Reintegrating Employees Undergoing Cancer Treatment into the Workplace: A Qualitative Study of Employer and Co-worker Perspectives.

Purpose The purpose of this study was to explore how employers and co-workers experience the return to work (RTW) process of employees undergoing cancer treatment. Methods Sixteen semi-structured individual interviews and participant observations at seven workplaces took place, involving seven employers and nine co-workers with different professions. A phenomenological-hermeneutic analytic approach was applied involving coding, identification of themes, and interpretation. Results We identified three employer themes: call for knowledge, Making decisions, and Feeling helpless. Also, three co-worker themes were identified: understanding and sympathy, extra work and burden, and Insecurity about future work tasks. Early initiated RTW, e.g. less work hours and work accommodations, did neither constitute challenges for employers nor co-workers in the beginning of the RTW process. However, when the RTW process was prolonged employers encountered difficulties in finding suitable work tasks, whereas co-workers were burdened by extra work. Conclusions Overall, cancer survivors' RTW process was welcomed and encouraged at the workplace level. However, employer and co-worker experiences suggested that RTW initiation parallel with cancer treatment raised challenges at the workplace level, when the RTW process was extended beyond the initial RTW plan; increased workload and difficulties in balancing the needs of the cancer survivor and co-workers. Mechanisms that support cancer survivors' RTW without introducing strain on co-workers should be investigated in future research. Furthermore, support for employers in their RTW management responsibilities needs to be addressed in general and in particular in future RTW interventions.

Iron deficiency and preoperative anaemia in patients scheduled for elective hip- and knee arthroplasty - an observational study.

BACKGROUND AND OBJECTIVES: Preoperative anaemia is prevalent in elderly patients scheduled for major orthopaedic surgery and is associated with increased transfusion risk and postoperative morbidity. New guidelines recommend preoperative correction of anaemia and iron deficiency in all patients with a Hb < 13 g/dl. However, iron deficiency and other causes of preoperative anaemia in hip- (THA) and knee (TKA) arthroplasty are only sparsely studied. MATERIALS AND METHODS: Preoperative Hb and iron status were prospectively collected from 882 unselected elective fast-track THA/TKA patients and analysed according to both WHO anaemia criteria (Hb < 12 g/dl females, <13 g/dl males) and Hb < 13 g/dl for both genders. Iron deficiency (ID) and other possible anaemia causes were classified by ferritin, transferrin saturation, P-cobalamin, P-folate, C-reactive protein and creatinine. RESULTS: Ninety-five (10·8%) and 243 (27·6%) of the study population were WHO anaemic or had a Hb < 13 g/dl, respectively. Transfusion was more common in anaemic vs. non-anaemic patients 43 vs. 13%; (P < 0·001), and in patients with Hb < 13 g/dl vs. Hb > 13 g/dl 28 vs. 11% (P < 0·001). 154 (17·5%) of all patients had ID, and ID was the most common cause of anaemia with a prevalence of 41% in WHO anaemic patients and 33% in patients with Hb < 13 g/dl. A further 19 (20%) and 46 (19%) patients, respectively, had evidence of iron sequestration. CONCLUSION: Anaemia is prevalent prior to THA and TKA with iron deficiency as the most common and reversible cause.