A genome-wide test for paternal indirect genetic effects on lifespan in Drosophila melanogaster.

Exposing sires to various environmental manipulations has demonstrated that paternal effects can be non-trivial also in species where male investment in offspring is almost exclusively limited to sperm. Whether paternal effects also have a genetic component (i.e. paternal indirect genetic effects (PIGEs)) in such species is however largely unknown, primarily because of methodological difficulties separating indirect from direct effects of genes. PIGEs may nevertheless be important since they have the capacity to contribute to evolutionary change. Here we use Drosophila genetics to construct a breeding design that allows testing nearly complete haploid genomes (more than 99%) for PIGEs. Using this technique, we estimate the variance in male lifespan due to PIGEs among four populations and compare this to the total paternal genetic variance (the sum of paternal indirect and direct genetic effects). Our results indicate that a substantial part of the total paternal genetic variance results from PIGEs. A screen of 38 haploid genomes, randomly sampled from a single population, suggests that PIGEs also influence variation in lifespan within populations. Collectively, our results demonstrate that PIGEs may constitute an underappreciated source of phenotypic variation.

The Effect of Parental Loss on Social Mobility in Early Twentieth-Century Sweden.

Parents are assumed to play a crucial role in the socioeconomic attainment of children. Through investments of both time and resources, they promote the ability, human capital, networks, and motivation of their children to advance socially, or at least to maintain their social position. Consequently, losing a parent in childhood could be detrimental to adult socioeconomic outcomes. We use full-count linked census data and a comprehensive death register to study the effect of parental loss on socioeconomic outcomes in adulthood in Sweden during the first half of the twentieth century. We employ sibling fixed-effects models and the Spanish flu as an exogenous mortality shock to assess the importance of endogeneity bias in associations between parental loss and socioeconomic outcomes. Maternal death led to worse socioeconomic outcomes in adulthood in terms of occupational and class attainment, as well as for social mobility. The effects seem to be causal but the magnitudes were small. For paternal death, we find no consistent pattern, and in most models there was no effect on sons' socioeconomic outcomes. The patterns were similar for sons and daughters and do not support the theory that parental loss had important negative effects on socioeconomic outcomes in adulthood.

The impact of kin proximity on net marital fertility and maternal survival in Sweden 1900-1910-Evidence for cooperative breeding in a societal context of nuclear families, or just contextual correlations?

OBJECTIVE: We investigate the association between the geographic proximity of the grandparents on net marital fertility and maternal survival in Sweden, 1900-1910, within the framework of the cooperative-breeding-hypothesis. METHODS: Data were derived from Swedish full-count censuses (1880-1910) and the Swedish Death Index. Married couples were linked to their parental households. Poisson and logistic regression analyses were used to investigate the association between the geographical proximity of the grandparents on net marital fertility, which we measured as the number of surviving children born between 1900 and 1910, and the mother's survival. Models were fitted with and without fixed effects to assess the effects of unobserved characteristics shared at the parish and the family level. RESULTS: The results indicate that net fertility and maternal survival increased with the husband's parents' geographic proximity. In contrast, we found no evidence that the geographic proximity of the wife's parents was associated with increased fertility or maternal survival. Rather, the presence of the mother's parents in the household lowered net fertility and reduced maternal survival. CONCLUSIONS: This study provides evidence that kin proximity was associated with fertility and mortality of married women, and that the associations differed for paternal and maternal kin in the societal context of Swedish nuclear families (1900-1910). However, the patterns of kin proximity that we identified were correlated with characteristics such as socioeconomic status, occupation, and wealth, which also exhibited strong correlations with fertility and survival. Future research assessing the effects of kinship on demographic developments must therefore carefully consider the socio-environmental context.

Reorganization of heart failure management and improved outcome - the 4D HF Project.

OBJECTIVES: Heart failure (HF) management is suboptimal in Sweden despite available evidence-based guidelines. To improve HF treatment, a comprehensive HF management program (4D project) was implemented in the Stockholm County (>2.1 million inhabitants). Design. A standardized care program centralized at five hospital-based HF clinics was implemented in 2014-2017. We registered from 2012 to 2017: (1) numbers of referrals and visits to HF clinics, (2) numbers of hospital admitted patients per million inhabitants, (3) dispensed HF medications after admission, and (4) covariate-adjusted 1-year all-cause mortality or HF readmission. Results. Yearly visits to the five HF outpatient clinics increased 3.4 times from 3,372 to 11,527. Dispensed HF drug prescriptions increased, in particular, for readmitted patients, compared to 2012 (p<.0001). Total number of hospital admitted HF patients as well as new-onset or readmitted HF patients decreased by 16, 13, and 20%, respectively (p < .0001). The combined 1-year mortality or HF readmission over the period was 48% (n = 17,124/35,880) and improved per year (HR 0.98 [0.97-0.99], p < .001) from 2012. Conclusion. A comprehensive standardized care HF management program including expanded HF clinics was associated with improved evidence-based medication, reduced HF hospitalization, and improvement of the combined outcome of 1-year mortality or HF readmission in Stockholm.

Epidemiology and control of meticillin-resistant Staphylococcus aureus in Stockholm County, Sweden, 2000 to 2016: overview of a "search-and-contain" strategy.

To review the epidemiology and measures to control meticillin-resistant Staphylococcus aureus, MRSA, in Stockholm between 2000 and 2016 from the perspective of the Department of Communicable Disease Control and Prevention, Stockholm County Council, Sweden. Age, sex, and place of acquisition of their MRSA on all patients reported to the department were reviewed. Measures for control included surveillance through mandatory reporting of cases, screening patients with risk factors for MRSA, strict adherence to basic nursing hygienic principles, isolation of MRSA positive patients in single rooms in dedicated MRSA wards, and cohorting of staff. An MRSA team was created at the Department of Infectious Diseases, Karolinska University Hospital, for follow-up of all cases. Several administrative meetings and cooperative groups were formed that are still in function. From 2000 to 2016, there were 7373 MRSA cases reported. Healthcare-associated MRSA, HA-MRSA, was successfully controlled, and from 2006 onwards, very limited HA-MRSA transmission or outbreaks occurred. However, incidence increased overall, from 9.5 per 100,000 in 2000 to 37.3 per 100,000 in 2016, due to increase of MRSA acquired abroad and of MRSA acquired in the Swedish community. Surveillance and control measures have been successful in containing HA-MRSA in Stockholm, Sweden, but incidence has increased substantially due to imported cases and spread in the Swedish community. The strategy may be termed "search-and-contain" since screening, infection control, follow-up, and advice on personal hygiene were cornerstones of control, whereas eradication of carriage was not.

Limited value of NT-proBNP as a prognostic marker of all-cause mortality in patients with heart failure with preserved and mid-range ejection fraction in primary care: A report from the swedish heart failure register.

Aim: The prognostic value of natriuretic peptides in the management of heart failure (HF) patients with ejection fraction (EF) <40% is well established, but is less known for those with EF ≥40% managed in primary care (PC). Therefore, the aim of this study is to describe the prognostic significance of plasma NT-proBNP in such patients managed in PC.Subjects: We included 924 HF patients (48% women) with EF ≥40% and NT-proBNP registered in the Swedish Heart Failure Registry. Follow-up was 1100 ± 687 days.Results: One-, three- and five-year mortality rates were 8.1%, 23.9% and 44.7% in patients with EF 40-50% (HFmrEF) and 7.3%, 23.6% and 37.2% in patients with EF ≥50% (HFpEF) (p = 0.26). Patients with the highest mean values of NT-proBNP had the highest all-cause mortality but wide standard deviations (SDs). In univariate regression analysis, there was an association only between NT-proBNP quartiles and all-cause mortality. In HFmrEF patients, hazard ratio (HR) was 1.96 (95% CI 1.60-2.39) p < 0.0001) and in HFpEF patients, HR was 1.72 (95% CI 1.49-1.98) p < 0.0001). In a multivariate Cox proportional hazard regression analysis, adjusted for age, NYHA class, atrial fibrillation and GFR class, this association remained regarding NT-proBNP quartiles [HR 1.83 (95% CI 1.38-2.44), p < 0.0001] and [HR 1.48 (95% CI 1.16-1.90), p = 0.0001], HFmrEF and HFpEF, respectively.Conclusion: NT-proBNP has a prognostic value in patients with HF and EF ≥40% managed in PC. However, its clinical utility is limited due to high SDs and the fact that it is not independent in this population which is characterized by high age and much comorbidity.Key pointsIt is uncertain whether NT-proBNP predicts risk in heart failure with preserved ejection fraction (EF > 40%, HFpEF) managed in primary care.We show that high NT-proBNP predicts increased all-cause mortality in HFpEF-patients managed in primary care.The clinical use is however limited due to large standard deviations, many co-morbidities and high age.Many of these co-morbidities contribute to all-cause mortality and management of these patients should also focus on these co-morbidities.

Social Class and Excess Mortality in Sweden During the 1918 Influenza Pandemic.

Consensus is lacking in the literature about the role of socioeconomic factors on influenza-associated deaths during the 1918 pandemic. Although some scholars have found that social factors were important, others have not. In this study, we analyzed differences in excess mortality by social class in Sweden during the 1918 pandemic. We analyzed individual-level mortality of the entire population aged 30-59 years by combining information from death records with census data on occupation. Social class was measured by an occupation-based class scheme. Excess mortality during the pandemic was measured as the number of deaths relative to the number occurring in the same month the year before. Social class differences in numbers of deaths were modeled using a complementary log-log model that was adjusted for potential confounding at the family, the residential (urban/rural), and the county levels. We found notable class differences in excess mortality but no perfect class gradient. Class differences were somewhat larger for men than for women.

Upregulation of Plasminogen Activator Inhibitor-1 in Irradiated Recipient Arteries and Veins from Free Tissue Transfer Reconstruction in Cancer Patients.

BACKGROUND: Clinical studies have shown that radiotherapy can induce vascular disease at the site of exposure but is usually not clinically evident until years after treatment. We have studied irradiated human arteries and veins to better understand the underlying biology in search of future treatments. The aim was to investigate whether radiotherapy contributed to a sustained expression of plasminogen activator inhibitor-1 (PAI-1) in human arteries and veins. METHODS: Irradiated arteries and veins were harvested, together with unirradiated control vessels, from patients undergoing free tissue transfer reconstruction at a median time of 90 weeks [5-650] following radiation exposure. Differential gene expression of PAI-1 was analysed, together with immunohistochemistry (IHC) and immunofluorescence (IF). RESULTS: PAI-1 gene expression was increased in both arteries (p = 0.012) and veins (p < 0.001) in irradiated compared to unirradiated control vessels. IHC and IF indicated that cells expressing PAI-1 were located in the adventitia of both arteries and veins and colocalized with cells positive for CD68, CD45, and α-SMA in arteries and with CD45 and α-SMA in veins. CONCLUSION: The current study shows a sustained upregulation of PAI-1 in both arteries and veins after exposure to ionizing radiation, indicating a chronic inflammation mainly in the adventitia. We believe that the results contribute to further understanding of radiation-induced vascular disease, where targeting PAI-1 may be a potential treatment.

Gas phase composition of a NiMH battery during a work cycle.

Side reactions leading to gas evolution are undesirable in batteries and result in reduced coulombic efficiency and shortened lifetime. Quantitative analysis of the gases that evolve is therefore important to improve understanding of the reactions occurring in the battery during cycling and could be used to optimize battery operation. However, the measurements are challenging because batteries are by their nature closed with limited gas space. Nickel metal hydride (NiMH) batteries are widely used due to their good rate capability, reliability, and environmental friendliness. The battery type has been extensively studied in terms of degradation and performance. However, very few studies have been conducted on the gas composition created during a work cycle. In this study, two methods for investigating the internal NiMH battery gas phase composition during different charge/discharge cycles using a mass spectrometer (MS) were developed. In the first method, the battery module was connected by a sampler system. In the second method, the battery was connected directly using a microcapillary, and the gas composition was continuously measured. In addition to the gas composition, the voltage, pressure, and temperature of the battery were recorded. The most abundant component in the measured gas phase was nitrogen, present in the cell from the assembly stage, followed by hydrogen. A clear rising trend of hydrogen pressure as depth of charge (DOC) increased was recorded, while oxygen levels were low except around the end of charge. The methods were found to be a reliable means of investigating NiMH gas composition without negatively affecting the battery and may be adapted to other battery chemistries.

[The reporting of adverse drug reactions has been working well during the pandemic - but there is room for improvement]. / Spontanrapporteringen har fyllt sitt syfte under pandemin.

Reporting of suspected adverse drug reactions (ADRs), from healthcare professionals and from consumers, contributes to early detection of new safety risks with medicines. The reporting of adverse reactions has been working well during the pandemic but indicates at the same time a significant under-reporting (hidden statistics). The propensity to report clearly increases with enhanced communication. Consumer reports are an important complement to reports from health care professionals and contribute to valuable insights both within regulatory follow-up and research. Reporting of suspected ADRs is an important source that needs to be supplemented with other data sources for causality analysis. For reporting of suspected adverse reactions to continue to be a valuable tool in the search for new signals, we need to develop sustainable reporting systems and communication channels that meet our various needs in close cooperation between authorities and other actors.

Frequent colonization of betahaemolytic streptococci at various body sites including the perineum and anal canal during erysipelas and cellulitis.

Background: Erysipelas and cellulitis are usually caused by betahaemolytic streptococci but the aetiology is often difficult to verify in clinical practice. Methods: Patients with erysipelas or cellulitis were analysed for betahaemolytic streptococci in samples from multiple body sites, including the perineum and the anal canal, during the acute episode and at follow up. Healthy control persons were sampled from the same sites. Results: Betahaemolytic streptococci group A, C or G were identified in 23/28 (82%) patients, most commonly group G. A wound or ulcer, present in 16/28 (57%), was colonized in 8/16 (50%). The perineum and anal canal were colonized in 11/28 (39%) and 10/28 (36%), respectively. At follow-up after about 4 weeks, only 4/28 (14%) were colonized (p<.001). In 39 healthy control persons, no betahaemolytic streptococci group A were found, groups C or G were found in 4/39 (10%). Group B streptococci were more often identified in controls, than in patients,12/39 (31%). Conclusions: Acute episodes of erysipelas or cellulitis are associated with colonization of betahaemolytic streptococci at multiple sites including the perineum and anal canal, in particular serogroup G. This may be important for choice of primary antibiotic therapy and possibilities for prevention of relapses.

Fuel Cell Measurements with Cathode Catalysts of Sputtered Pt3 Y Thin Films.

Fuel cells are foreseen to have an important role in sustainable energy systems, provided that catalysts with higher activity and stability are developed. In this study, highly active sputtered thin films of platinum alloyed with yttrium (Pt3 Y) are deposited on commercial gas diffusion layers and their performance in a proton exchange membrane fuel cell is measured. After acid pretreatment, the alloy is found to have up to 2.5 times higher specific activity than pure platinum. The performance of Pt3 Y is much higher than that of pure Pt, even if all of the alloying element was leached out from parts of the thin metal film on the porous support. This indicates that an even higher performance is expected if the structure of the Pt3 Y catalyst or the support could be further improved. The results show that platinum alloyed with rare earth metals can be used as highly active cathode catalyst materials, and significantly reduce the amount of platinum needed, in real fuel cells.

The Holocene retreat dynamics and stability of Petermann Glacier in northwest Greenland.

Submarine glacial landforms in fjords are imprints of the dynamic behaviour of marine-terminating glaciers and are informative about their most recent retreat phase. Here we use detailed multibeam bathymetry to map glacial landforms in Petermann Fjord and Nares Strait, northwestern Greenland. A large grounding-zone wedge (GZW) demonstrates that Petermann Glacier stabilised at the fjord mouth for a considerable time, likely buttressed by an ice shelf. This stability was followed by successive backstepping of the ice margin down the GZW's retrograde backslope forming small retreat ridges to 680 m current depth (∼730-800 m palaeodepth). Iceberg ploughmarks occurring somewhat deeper show that thick, grounded ice persisted to these water depths before final breakup occurred. The palaeodepth limit of the recessional moraines is consistent with final collapse driven by marine ice cliff instability (MICI) with retreat to the next stable position located underneath the present Petermann ice tongue, where the seafloor is unmapped.

PAN-AMPK activator O304 improves glucose homeostasis and microvascular perfusion in mice and type 2 diabetes patients.

AMPK activated protein kinase (AMPK), a master regulator of energy homeostasis, is activated in response to an energy shortage imposed by physical activity and caloric restriction. We here report on the identification of PAN-AMPK activator O304, which - in diet-induced obese mice - increased glucose uptake in skeletal muscle, reduced ß cell stress, and promoted ß cell rest. Accordingly, O304 reduced fasting plasma glucose levels and homeostasis model assessment of insulin resistance (HOMA-IR) in a proof-of-concept phase IIa clinical trial in type 2 diabetes (T2D) patients on Metformin. T2D is associated with devastating micro- and macrovascular complications, and O304 improved peripheral microvascular perfusion and reduced blood pressure both in animals and T2D patients. Moreover, like exercise, O304 activated AMPK in the heart, increased cardiac glucose uptake, reduced cardiac glycogen levels, and improved left ventricular stroke volume in mice, but it did not increase heart weight in mice or rats. Thus, O304 exhibits a great potential as a novel drug to treat T2D and associated cardiovascular complications.

Improved Head and Neck Free Flap Outcome-Effects of a Treatment Protocol Adjustment from Pre- to Postoperative Radiotherapy.

BACKGROUND: The impact of preoperative radiotherapy on microvascular reconstructive surgery outcome has been a subject of debate. However, data are conflicting and often dependent on local treatment protocols. We have studied the effects of radiotherapy in a unique, single-center setting where a treatment protocol change was undertaken from pre- to postoperative radiotherapy administration for microsurgical head and neck reconstructions. METHODS: A cohort study was conducted for 200 consecutive head and neck free flap cases, where 100 were operated on before and 100 after the treatment protocol adjustment in 2006. Only direct cancer reconstructions were included. Complication rates of anastomosis-related (flap necrosis) and flap bed-related (infection, fistula, and wound dehiscence) complications were compared between irradiated and nonirradiated patients. A multivariate analysis was performed to correct for treatment period. RESULTS: One hundred twenty-six patients had received radiotherapy before reconstruction due to cases of cancer recurrence. There were no significant differences in demographic data or risk factors between irradiated and nonirradiated cases. Irradiated cases had a higher rate of both flap loss (9.5% versus 1.4%; P = 0.034) and flap bed-related complications (29% versus 13%; P = 0.014). However, after multivariate analysis, there was only a significant relationship between preoperative irradiation and infection (odds ratio = 2.51; P = 0.033) and fistula formation (odds ratio = 3.13; P = 0.034). CONCLUSIONS: The current single-center study clearly indicates that preoperative radiotherapy is a risk factor for both infection and fistula formation, most likely related to an impaired flap bed. We suggest postoperative radiotherapy administration whenever possible for oncological reasons, otherwise proper antibiotic cover and meticulous flap insetting to prevent radiation-related infection and fistula formation.

Flow splitting at the inlet electrode as a method for decreasing the electric current in electric field assisted liquid chromatography.

The combination of pressurized flow and electric field offers, with the use of capillary columns, several options for retention control. However, it has been shown that the utility of this technique is strongly limited by the high electric current that is generated at the high electric field strengths that are needed. We have earlier shown that the high current is a result of locally increased mobile phase ion concentration in the electric field, particularly around the inlet electrode. In this paper, we report that by splitting the mobile phase flow around the inlet electrode a relatively constant ion concentration around the electrode can be obtained and the high currents are there by reduced.

Germ line insertions of moloney murine leukemia virus in the TLL mouse causes site-specific differences in lymphoma/leukemia frequency and tumor immunophenotype.

BACKGROUND: Moloney murine leukemia virus (Mo-MLV) has proven valuable for studies of the pathogenesis of malignant lymphoma. Inoculation of newborn mice induces T cell lymphoma with 100% incidence. The TLL (T cell lymphoma/leukemia)-strain was previously established and was shown to spontaneously develop T cell lymphoma at high frequency. MATERIALS AND METHODS: Differential screening of cDNA libraries was performed to discover an involvement of Mo-MLV and genomic sequencing was used to identify the chromosomal position of Mo-ML V proviral integration sites. Immunophenotypes of the tumors were established by flow cytometty. Disease frequency curves were created according to the Kaplan-Meier method. RESULTS: Two independent Mo-MLV germ line integrations were characterized on chromosomes 2 and 14, giving rise to two substrains of mice denoted TLL-2 and TLL-14. The chromosomal position of the integrated provirus affected the frequency of disease, as well as the immunophenotype of the tumors. CONCLUSION: The data suggest that factors influencing the transcriptional activity of the chromosomal regions, leading to differences in proviral expression, could underlie the observed difference in tumor frequency.

U-EPX levels and wheezing in infants and young children with and without RSV bronchiolitis.

An association between severe infant bronchiolitis due to respiratory syncytial virus (RSV) and subsequent wheezing is well documented. High levels of urinary eosinophil protein X (U-EPX) have been related to active disease in asthmatic children. The aim of this study was to analyse whether RSV bronchiolitis leads to an increase in U-EPX levels and whether wheezing is more common in children with high U-EPX values. Seventeen infants requiring in-ward care for verified RSV lower respiratory tract infection were followed and compared with age-matched controls. A reference group without a history of RSV bronchiolitis was also included. At inclusion at mean age 3.3 months and at follow-up at mean age 32.9 months, U-EPX levels were comparable in the RSV group. However, at follow-up at mean age 6.4 months, the RSV group had significantly increased levels of U-EPX compared with inclusion (median 167.8; range 46.2-470.7 vs. 122.8; 43.7-266.0 microg/mmol creatinine; P=0.023) and also significantly increased compared with the 6-month-old controls (167.8 vs. 93.0; 19.0-204.0 microg/mmol creatinine; P=0.0095). RSV infected subjects that experienced wheezing had significantly higher U-EPX values both at inclusion and at age 32.9 months than those who did not. Also, in the reference group (mean age 18.4 months), the children who had wheezed during the preceding year had higher U-EPX levels than those who had not wheezed. In conclusion, RSV bronchiolitis severe enough to require in-ward care produces a significant, but transient increase in U-EPX. Furthermore, a high U-EPX at baseline appears to be associated with an increased risk of future wheezing.