Does Prolonged Education Causally Affect Dementia Risk When Adult Socioeconomic Status Is Not Altered? A Swedish Natural Experiment in 1.3 Million Individuals.

Intervening on modifiable risk factors to prevent dementia is of key importance, since progress-modifying treatments are not currently available. Education is inversely associated with dementia risk, but causality and mechanistic pathways remain unclear. We aimed to examine the causality of this relationship in Sweden using, as a natural experiment, data on a compulsory schooling reform that extended primary education by 1 year for 70% of the population between 1936 and 1949. The reform introduced substantial exogenous variation in education that was unrelated to pupils' characteristics. We followed 18 birth cohorts (n = 1,341,842) from 1985 to 2016 (up to ages 79-96 years) for a dementia diagnosis in the National Inpatient and Cause of Death registers and fitted Cox survival models with stratified baseline hazards at the school-district level, chronological age as the time scale, and cohort indicators. Analyses indicated very small or negligible causal effects of education on dementia risk (main hazard ratio = 1.01, 95% confidence interval: 0.98, 1.04). Multiple sensitivity checks considering only compliers, the pre-/post- design, differences in health-care-seeking behavior, and the impact of exposure misclassification left the results essentially unaltered. The reform had limited effects on further adult socioeconomic outcomes, such as income. Our findings suggest that without mediation through adult socioeconomic position, education cannot be uncritically considered a modifiable risk factor for dementia.

Twisted Intramolecular Charge Transfer (TICT) Controlled by Dimerization: An Overlooked Piece of the TICT Puzzle.

Organic dyes have shown high efficiencies in solar cells, which is mainly attributed to the push-pull strategy present in such dyes upon attaching to the semiconductor surfaces. We deeply studied the fundamental photophysical properties of cyanoacrylic dyes, mostly the L1 dye, and found unique emission properties that depend on many factors such as the solvent polarity and the concentration of the dye and could present a complete emission picture about this family of dyes. The L1 dye shows an intramolecular charge transfer (ICT) emission state at low concentrations (approximately nanomolar scale) and shows a twisted intramolecular charge transfer (TICT) emission state in specific solvents upon increasing the concentration to the micromolar scale. Moreover, the associated emission lifetimes of the ICT and TICT states of the L1 dye depend on solvent basicity, highlighting the role of hydrogen bond formation on controlling such states. Density functional theory calculations are performed to gain insight into the photophysical properties of the dye and revealed that H-bonding between the carboxylic groups triggers the dimerization at low concentrations. Using femtosecond transient absorption, we assigned the rate of TICT formation to be in the range (160-650 fs)-1, depending on the size of the studied cyanoacrylic dye. Therefore, we add herein a new dimension for controlling the formation of the TICT state, in addition to the solvent polarity and acceptor strength parameters. These findings are not limited to the studied dyes, and we expect that numerous organic carboxylic acids dyes show similar properties.

A comparison of the in vitro effects of three fibrinogen concentrates on clot strength in blood samples from cardiac surgery patients.

BACKGROUND: Fibrinogen concentrate is used clinically to improve hemostasis in bleeding patients. We investigated and compared the efficacy of three commercially available fibrinogen concentrates to improve clot strength in blood samples from cardiac surgery patients. OBJECTIVES: Postoperative blood samples were collected from 23 cardiac surgery patients. Samples were each divided into four vials, each supplemented with 1.125 mg of fibrinogen of one of three fibrinogen concentrates (RiaSTAP® , Fibryga® , FibCLOT® ), or placebo. The fibrinogen dose corresponded to 2.5 g per 70 kg of body weight. Clot strength after supplementation was assessed in duplicate with rotational thromboelastometry (ROTEM® ) using FIBTEM maximum clot firmness, EXTEM clot formation time, and maximum clot firmness assays. RESULTS: In vitro fibrinogen concentrate supplementation of the samples resulted in higher plasma fibrinogen concentrations and improved clot strength with all three concentrates. Supplementation with FibCLOT increased FIBTEM maximum clot firmness (+46% [25th-75th percentile 35-55] compared to placebo) significantly more than did supplementation with Fibryga (+26% [21-35]) and RiaSTAP (+29% [22-47], p < .001). FibCLOT supplementation also shortened EXTEM clot formation time and increased EXTEM maximum clot firmness to a greater extent than did the other concentrates (both p < .001). CONCLUSIONS: At the selected dose, FibCLOT was more effective than Fibryga and RiaSTAP in restoring clot strength in postoperative blood samples from cardiac surgery patients. These results may have implications for the choice of fibrinogen concentrate and dosing.

Secondary prevention medications after coronary artery bypass grafting and long-term survival: a population-based longitudinal study from the SWEDEHEART registry.

AIMS: To evaluate the long-term use of secondary prevention medications [statins, ß-blockers, renin-angiotensin-aldosterone system (RAAS) inhibitors, and platelet inhibitors] after coronary artery bypass grafting (CABG) and the association between medication use and mortality. METHODS AND RESULTS: All patients who underwent isolated CABG in Sweden from 2006 to 2015 and survived at least 6 months after discharge were included (n = 28 812). Individual patient data from SWEDEHEART and other mandatory nationwide registries were merged. Multivariable Cox regression models using time-updated data on dispensed prescriptions were used to assess associations between medication use and long-term mortality. Statins were dispensed to 93.9% of the patients 6 months after discharge and to 77.3% 8 years later. Corresponding figures for ß-blockers were 91.0% and 76.4%, for RAAS inhibitors 72.9% and 65.9%, and for platelet inhibitors 93.0% and 79.8%. All medications were dispensed less often to patients ≥75 years. Treatment with statins [hazard ratio (HR) 0.56, 95% confidence interval (95% CI) 0.52-0.60], RAAS inhibitors (HR 0.78, 95% CI 0.73-0.84), and platelet inhibitors (HR 0.74, 95% CI 0.69-0.81) were individually associated with lower mortality risk after adjustment for age, gender, comorbidities, and use of other secondary preventive drugs (all P < 0.001). There was no association between ß-blockers and mortality risk (HR 0.97, 95% CI 0.90-1.06; P = 0.54). CONCLUSION: The use of secondary prevention medications after CABG was high early after surgery but decreased significantly over time. The results of this observational study, with inherent risk of selection bias, suggest that treatment with statins, RAAS inhibitors, and platelet inhibitors is essential after CABG whereas the routine use of ß-blockers may be questioned.

The risk of dementia after coronary artery bypass grafting in relation to age and sex.

INTRODUCTION: We examined the long-term risk of dementia after coronary artery bypass grafting (CABG) in relation to age and sex. METHODS: All CABG patients in Sweden 1992-2015 (n = 111,335), and matched controls (n = 222,396) were included in a population-based study. Adjusted hazard ratios (aHR) for all-cause dementia, vascular dementia, and Alzheimer's disease were calculated. RESULTS: There was no difference in the risk for all-cause dementia between CABG patients and control subjects (aHR 0.98 [95% confidence interval 0.95 to 1.02]). CABG patients <65 years and 65 to 74 years had higher risk (aHR 1.29 [1.17-1.42] and 1.08 [1.02-1.13], respectively), and patients ≥75 years had lower risk (aHR 0.76 [0.71-0.81]). The highest risk was observed in women <65 years (aHR 1.64 [1.31-2.05]). DISCUSSION: Overall, the long-term risk for all-cause dementia does not differ between CABG patients and the general population. Younger patients have a higher risk, while older patients have a lower risk, compared to controls.

Regional fire scenarios in Spain: Linking landscape dynamics and fire regime for wildfire risk management.

Fire scenarios are multiscale land-type planning units for a fire regime with different applications at national, regional, and local scales. The main aim of this research is to implement a methodology integrating landscape dynamics and wildfire risk from a context-specific approach, to identify current fire scenarios at a regional scale in the Spanish Central Mountain Range. These homogeneous areas are linked to different stages of a territorial dynamics model called wildfire generations and related to land use diversity and land management trends. A place-based methodology has been developed to characterize fire scenarios using Geographic Information Systems and statistical analysis, resulting in analytical and diagnostic mapping that can be used as a decision support tool for spatial planning and wildfire risk management. Its implementation has led to the delimitation of 91 discrete geographic units in the Central Mountain Range, classified according to wildfire generations and land use-land cover criteria. In conclusion, the fire scenarios concept is a potential approach to manage uncertainty by moving from the operational level of fire suppression to the strategic level of integrated fire management.

Assessment of sample preparation methods for metaproteomics of extracellular proteins.

Enzyme discovery in individual strains of microorganisms is compromised by the limitations of pure culturing. In principle, metaproteomics allows for fractionation and study of different parts of the protein complement but has hitherto mainly been used to identify intracellular proteins. However, the extracellular environment is also expected to comprise a wealth of information regarding important proteins. An absolute requirement for metaproteomic studies of protein expression, and irrespective of downstream methods for analysis, is that sample preparation methods provide clean, concentrated and representative samples of the protein complement. A battery of methods for concentration, extraction, precipitation and resolubilization of proteins in the extracellular environment of a constructed microbial community was assessed by means of 2D gel electrophoresis and image analysis to elucidate whether it is possible to make the extracellular protein complement available for metaproteomic analysis. Most methods failed to provide pure samples and therefore negatively influenced protein gel migration and gel background clarity. However, one direct precipitation method (TCA-DOC/acetone) and one extraction/precipitation method (phenol/methanol) provided complementary high quality 2D gels that allowed for high spot detection ability and thereby also spot detection of less abundant extracellular proteins.

Careful in the Crisis? Determinants of Older People's Informal Care Receipt in Crisis-Struck European Countries.

Macroeconomic downturns can have an important impact on the receipt of informal and formal long-term care, because recessions increase the number of unemployed and affect net wealth. This paper investigates how the market for informal care changed during and after the Great Recession in Europe, with particular focus on the determinants of care receipt. We use data from the Survey of Health, Ageing and Retirement in Europe, which includes a rich set of variables covering waves before and after the Great Recession. We find evidence of an increase in the availability of informal care after the economic downturn when controlling for year and country fixed effects. This trend is mainly driven by changes in care provision of individuals not cohabiting with the care recipient. We also find evidence of several determinants of informal care receipt changing during the crisis - such as physical needs, personal wealth, and household structures. Copyright © 2016 John Wiley & Sons, Ltd.

Applying theories of microbial metabolism for induction of targeted enzyme activity in a methanogenic microbial community at a metabolic steady state.

Novel enzymes that are stable in diverse conditions are intensively sought because they offer major potential advantages in industrial biotechnology, and microorganisms in extreme environments are key sources of such enzymes. However, most potentially valuable enzymes are currently inaccessible due to the pure culturing problem of microorganisms. Novel metagenomic and metaproteomic techniques that circumvent the need for pure cultures have theoretically provided possibilities to identify all genes and all proteins in microbial communities, but these techniques have not been widely used to directly identify specific enzymes because they generate vast amounts of extraneous data.In a first step towards developing a metaproteomic approach to pinpoint targeted extracellular hydrolytic enzymes of choice in microbial communities, we have generated and analyzed the necessary conditions for such an approach by the use of a methanogenic microbial community maintained on a chemically defined medium. The results show that a metabolic steady state of the microbial community could be reached, at which the expression of the targeted hydrolytic enzymes were suppressed, and that upon enzyme induction a distinct increase in the targeted enzyme expression was obtained. Furthermore, no cross talk in expression was detected between the two focal types of enzyme activities under their respective inductive conditions. Thus, the described approach should be useful to generate ideal samples, collected before and after selective induction, in controlled microbial communities to clearly discriminate between constituently expressed proteins and extracellular hydrolytic enzymes that are specifically induced, thereby reducing the analysis to only those proteins that are distinctively up-regulated.

Getting the right tail right: Modeling tails of health expenditure distributions.

Health expenditure data almost always include extreme values, implying that the underlying distribution has heavy tails. This may result in infinite variances as well as higher-order moments and bias the commonly used least squares methods. To accommodate extreme values, we propose an estimation method that recovers the right tail of health expenditure distributions. It extends the popular two-part model to develop a novel three-part model. We apply the proposed method to claims data from one of the biggest German private health insurers. Our findings show that the estimated age gradient in health care spending differs substantially from the standard least squares method.

Betablockers and clinical outcome after surgical aortic valve replacement-a report from the SWEDEHEART registry.

OBJECTIVES: Previous reports suggest that betablockers appear non-beneficial after surgical aortic valve replacement (SAVR). This study aims to clarify the associations between betablockers and long-term outcome after SAVR. METHODS: All patients with isolated SAVR due to aortic stenosis in Sweden between 2006 and 2020, alive at six months after surgery, were included. Patients were identified in the SWEDEHEART registry and records were merged with data from three other mandatory national registries. Association between dispensed betablockers and MACE (all-cause mortality, myocardial infarction, stroke) was analyzed using Cox proportional hazards models, with time-updated data on medication and adjusted for age, sex, and comorbidities at baseline. RESULTS: In total, 11849 patients were included (median follow-up 5.4 years [range 0-13.5]). Betablockers were prescribed to 79.7% of patients at baseline, decreasing to 62.2% after 5 years. Continuing treatment was associated with higher risk of MACE (adjusted hazard ratio 1.14 [95% confidence interval 1.05-1.23]). The association was consistent over subgroups based on age, sex, and comorbidities except atrial fibrillation (HR 1.05 [95% CI 0.93-1.19]). A sensitivity analysis including time-updated data on comorbidites attenuated the difference between the groups (HR 1.04 [95% CI 0.95-1.14, p = 0.33]). CONCLUSIONS: Treatment with betablockers did not appear to be associated with inferior long-term outcome after SAVR, when adjusting for new concomitant diseases. Thus, it is likely that it is the underlying cardiac diseases that are associated with MACE rather than betablocker treatment.

Sampling conditions influence multiple electrode platelet aggregometry in cardiac surgery patients.

OBJECTIVES: To investigate the importance of blood sampling conditions for multiple electrode platelet aggregometry (MEA) in cardiac surgery patients. DESIGN: Eighty-one patients undergoing first time CABG surgery were included in three prospective, observational studies. MEA was used to analyze platelet aggregability after addition of adenosine-diphosphate (ADP) or thrombin activating peptide 6 (TRAP). In substudy 1, hirudin and citrate tubes were compared. In substudy 2, samples from peripheral vein, central venous catheter, and radial artery were compared and in substudy 3, the effect of surgery was investigated by analyzing pre- and postoperative samples. RESULTS: Platelet aggregability values were 30% higher in hirudin tubes than in citrate tubes. There was a significant correlation between hirudin and citrate tubes in TRAP-induced aggregability (r = 0.84, p < 0.001) but not in ADP-induced aggregability (r = 0.25, p = 0.13). The blood sampling site did not influence platelet aggregability. Surgery reduced ADP-induced aggregability by 31% (p < 0.001) and TRAP-induced aggregability by 30% (p < 0.001) with large intraindividual variations. CONCLUSIONS: MEA results in cardiac surgery patients should not be compared between samples collected in test tubes with different anticoagulants. The choice of blood sampling site does not affect the results. The operation in itself reduces markedly mean platelet aggregability.

Dye-sensitized solar cells employing a SnO2-TiO2 core-shell structure made by atomic layer deposition.

This paper describes the synthesis and characterization of core-shell structures, based on SnO2 and TiO2, for use in dye-sensitized solar cells (DSC). Atomic layer deposition is employed to control and vary the thickness of the TiO2 shell. Increasing the TiO2 shell thickness to 2 nm improved the device performance of liquid electrolyte-based DSC from 0.7% to 3.5%. The increase in efficiency originates from a higher open-circuit potential and a higher short-circuit current, as well as from an improvement in the electron lifetime. SnO2-TiO2 core-shell DSC devices retain their photovoltage in darkness for longer than 500 seconds, demonstrating that the electrons are contained in the core material. Finally core-shell structures were used for solid-state DSC applications using the hole transporting material 2,2',7,7',-tetrakis(N, N-di-p-methoxyphenyl-amine)-9,9',-spirofluorene. Similar improvements in device performance were obtained for solid-state DSC devices.

The performance of EuroSCORE II in CABG patients in relation to sex, age, and surgical risk: a nationwide study in 14,118 patients.

BACKGROUND: To determine the discriminative accuracy and calibration of EuroSCORE II in relation to age, sex, and surgical risk in a large nationwide coronary artery bypass grafting (CABG) cohort. METHODS: All 14,118 patients undergoing isolated CABG in Sweden during 2012-2017 were included. Individual patient data were taken from the SWEDEHEART registry. Patients were divided by age (< 60, 60-69, 70-79, ≥ 80 years), sex, and surgical risk (low: EuroSCORE < 4%, intermediate: 4-8%, high: > 8%). Discriminative accuracy was determined by the area under the receiver operating characteristic curve (AUC) and calibration by the observed/estimated (O/E) mortality ratio at 30 days. RESULTS: AUC and O/E ratio were 0.82 (95% CI 0.79-0.85) and 0.58 (0.50-0.66) overall, 0.82 (0.79-0.86) and 0.57 (0.48-0.66) in men, and 0.79 (0.73-0.85) and 0.60 (0.47-0.75) in women. Regarding age, discriminative accuracy was highest in patients aged 60-69 years (AUC: 0.86 [0.80-0.93]) but was satisfactory in all groups (AUC: 0.74-0.80). O/E ratio varied from 0.26 for patients > 60 years to 0.90 for patients > 80 years. Regarding surgical risk, AUC and O/E ratio were 0.63 (0.44-0.83) and 0.18 (0.09-0.30) in low-risk patients, 0.60 (0.55-0.66) and 0.57 (0.46-0.68) in intermediate-risk patients, and 0.78 (0.73-0.83) and 0.78 (0.64-0.92) in high-risk patients. CONCLUSIONS: EuroSCORE II had good discriminative accuracy independently of sex and age, but markedly overestimated mortality risk, especially in younger patients. Accuracy and calibration were better in high-risk patients than in low-risk and intermediate-risk patients.

Obstructive sleep apnea severity and prevalent atrial fibrillation in a sleep clinic cohort with versus without excessive daytime sleepiness.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with atrial fibrillation (AF) in cardiac cohorts. Less is known regarding the magnitude of this association in a sleep clinic cohort with vs. without excessive daytime sleepiness (EDS). OBJECTIVES: To explore the association of OSA severity with AF in a sleep clinic cohort stratified by EDS. PATIENTS AND METHODS: All consecutive adults (n = 3814) admitted to the Skaraborg Hospital, Sweden between Jan 2005 and December 2011 were registered in a local database, and the follow-up ended in December 2018. OSA was defined as an apnea-hypopnea index (AHI) ≥5 events/h. Mild OSA was defined as AHI ≥5 & AHI<15 events/h; moderate OSA as AHI ≥15 & AHI<30 events/h; and severe OSA as AHI ≥30 events/h. EDS was defined as an Epworth Sleepiness Scale score ≥11. We conducted cross-sectional analyzes of the prevalent AF across the OSA severity categories and logistic regression analyzes stratified by EDS. RESULTS: In all, 202 patients (5.3%) had AF at baseline, 1.6% in no-OSA, 3.9% in mild OSA, 5.2% in moderate OSA, and 7.6% in severe OSA, respectively (p < 0.001). The stratified analyzes revealed that patients with severe OSA without EDS had an increased risk for prevalent AF (OR 2.54, 95% CI 1.05-6.16; p = 0.039) independent of the confounding factors. CONCLUSIONS: There was an independent dose-response relationship between OSA and prevalent AF among the non-sleepy phenotype in this sleep clinic cohort. Since adherence to OSA treatment is challenging in the absence of EDS, these patients may have increased risk for adverse cardiovascular outcomes.

Comparing spiro-OMeTAD and P3HT hole conductors in efficient solid state dye-sensitized solar cells.

Two hole conductor materials, spiro-OMeTAD and P3HT, were compared in solid-state dye-sensitized solar cells. Two organic dyes containing one anchor unit (D35) or two anchor units (M3) were used in the comparison. Absorbed photon to current conversion efficiency close to unity was obtained for the devices with spiro-OMeTAD. Energy conversion efficiencies of 4.7% and 4.9% were measured for the devices with spiro-OMeTAD and the dyes D35 and M3, respectively. For the devices using the P3HT hole conductor the results were rather different comparing the two dye molecules, with energy conversion efficiencies of 3.2% and 0.5% for D35 and M3, respectively. Photo-induced absorption measurements suggest that the regeneration of the dyes, and the polymer infiltration, is not complete using P3HT, while spiro-OMeTAD regenerates the dyes efficiently. However, the TiO(2)/D35/P3HT system shows rather high energy conversion efficiency and electrochemical oxidation of the dyes on TiO(2) indicates that D35 have a more efficient dye to dye hole conduction than M3, which thereby might explain the higher performance. The dye hole conduction may therefore be of significant importance for optimizing the energy conversion in such hybrid TiO(2)/dye/polymer systems.

Long-term outcome of patients undergoing re-exploration for bleeding following cardiac surgery: a SWEDEHEART study.

OBJECTIVES: Excessive bleeding leading to re-exploration is a severe complication of cardiac surgical procedures, associated with early postoperative morbidity and mortality. Less is known about the long-term outcome of these patients. We evaluated the impact of re-exploration after cardiac surgery on peri- and postoperative morbidity and mortality, as well long-term mortality, in a well-defined nationwide population. METHODS: In this retrospective study, 48 060 consecutive patients undergoing coronary artery bypass grafting (CABG) and/or valve surgery from 2006 to 2015 were analysed. Multivariable logistic regression was used to identify factors associated with re-exploration, morbidity and mortality. Cox regression analysis was implemented to explore the association between re-exploration and long-term mortality. The mean follow-up time was 4.6 years (range 0-10 years) with follow-up time set at 31 December 2015. RESULTS: Overall, 2371 patients (4.9%) underwent re-exploration. Factors associated with re-exploration included advanced age, procedures other than isolated CABG and acute surgery. Re-explored patients had an increased risk of unadjusted mortality at 30, 90 and beyond 90 days (all P < 0.001). Significance was maintained after adjustment at 30 days [odds ratio: 3.94, 95% confidence interval (CI): 3.19-4.85, P < 0.001] and 90 days (odds ratio: 3.79, 95% CI: 3.14-4.55, P < 0.001), but not with long-term mortality (hazard ratio: 1.02, 95% CI: 0.91-1.15, P = 0.712). Furthermore, re-exploration was independently associated with other postoperative complications, e.g. prolonged hospital stay, stroke and renal injury. CONCLUSIONS: Patients who are re-explored for bleeding within 24 h have almost four-fold higher odds of mortality within 3 months post-procedure. However, the increased risk of death following re-exploration is not maintained in the long term.

Identifying targets for increased biogas production through chemical and organic matter characterization of digestate from full-scale biogas plants: what remains and why?

BACKGROUND: This study examines the destiny of macromolecules in different full-scale biogas processes. From previous studies it is clear that the residual organic matter in outgoing digestates can have significant biogas potential, but the factors dictating the size and composition of this residual fraction and how they correlate with the residual methane potential (RMP) are not fully understood. The aim of this study was to generate additional knowledge of the composition of residual digestate fractions and to understand how they correlate with various operational and chemical parameters. The organic composition of both the substrates and digestates from nine biogas plants operating on food waste, sewage sludge, or agricultural waste was characterized and the residual organic fractions were linked to substrate type, trace metal content, ammonia concentration, operational parameters, RMP, and enzyme activity. RESULTS: Carbohydrates represented the largest fraction of the total VS (32-68%) in most substrates. However, in the digestates protein was instead the most abundant residual macromolecule in almost all plants (3-21 g/kg). The degradation efficiency of proteins generally lower (28-79%) compared to carbohydrates (67-94%) and fats (86-91%). High residual protein content was coupled to recalcitrant protein fractions and microbial biomass, either from the substrate or formed in the degradation process. Co-digesting sewage sludge with fat increased the protein degradation efficiency with 18%, possibly through a priming mechanism where addition of easily degradable substrates also triggers the degradation of more complex fractions. In this study, high residual methane production (> 140 L CH4/kg VS) was firstly coupled to operation at unstable process conditions caused mainly by ammonia inhibition (0.74 mg NH3-N/kg) and/or trace element deficiency and, secondly, to short hydraulic retention time (HRT) (55 days) relative to the slow digestion of agricultural waste and manure. CONCLUSIONS: Operation at unstable conditions was one reason for the high residual macromolecule content and high RMP. The outgoing protein content was relatively high in all digesters and improving the degradation of proteins represents one important way to increase the VS reduction and methane production in biogas plants. Post-treatment or post-digestion of digestates, targeting microbial biomass or recalcitrant protein fractions, is a potential way to achieve increased protein degradation.

Global gene expression profiling of somatic motor neuron populations with different vulnerability identify molecules and pathways of degeneration and protection.

Different somatic motor neuron subpopulations show a differential vulnerability to degeneration in diseases such as amyotrophic lateral sclerosis, spinal muscular atrophy and spinobulbar muscular atrophy. Studies in mutant superoxide dismutase 1 over-expressing amyotrophic lateral sclerosis model mice indicate that initiation of disease is intrinsic to motor neurons, while progression is promoted by astrocytes and microglia. Therefore, analysis of the normal transcriptional profile of motor neurons displaying differential vulnerability to degeneration in motor neuron disease could give important clues to the mechanisms of relative vulnerability. Global gene expression profiling of motor neurons isolated by laser capture microdissection from three anatomical nuclei of the normal rat, oculomotor/trochlear (cranial nerve 3/4), hypoglossal (cranial nerve 12) and lateral motor column of the cervical spinal cord, displaying differential vulnerability to degeneration in motor neuron disorders, identified enriched transcripts for each neuronal subpopulation. There were striking differences in the regulation of genes involved in endoplasmatic reticulum and mitochondrial function, ubiquitination, apoptosis regulation, nitrogen metabolism, calcium regulation, transport, growth and RNA processing; cellular pathways that have been implicated in motor neuron diseases. Confirmation of genes of immediate biological interest identified differential localization of insulin-like growth factor II, guanine deaminase, peripherin, early growth response 1, soluble guanylate cyclase 1A3 and placental growth factor protein. Furthermore, the cranial nerve 3/4-restricted genes insulin-like growth factor II and guanine deaminase protected spinal motor neurons from glutamate-induced toxicity (P < 0.001, ANOVA), indicating that our approach can identify factors that protect or make neurons more susceptible to degeneration.

Disease and fertility: Evidence from the 1918-19 influenza pandemic in Sweden.

What are the consequences of a severe health shock like an influenza pandemic on fertility? Using rich administrative data and a difference-in-differences approach, we evaluate fertility responses to the 1918-19 influenza pandemic in Sweden. We find evidence of a small baby boom following the end of the pandemic, but we show that this effect is second-order compared to a strong long-term negative fertility effect. Within this net fertility decline there are compositional effects: we observe a relative increase in births to married women and to better-off families. Several factors - including disruptions to the marriage market and income effects - contribute to the long-term fertility reduction. The results are consistent with studies that find a positive fertility response following natural disasters, but we show that this effect is short-lived.