Trends in childhood body mass index between 1936 and 2011 showed that underweight remained more common than obesity among 398 970 Danish school children.

AIM: To examine trends in all body mass index (BMI) groups in children from 1936 to 2011. METHODS: We included 197 694 girls and 201 276 boys from the Copenhagen School Health Records Register, born between 1930 and 1996, with longitudinal weight and height measurements (6-14 years). Using International Obesity Task Force criteria, BMI was classified as underweight, normal-weight, overweight and obesity. Sex- and age-specific prevalences were calculated. RESULTS: From the 1930s, the prevalence of underweight was stable until a small increase occurred from 1950 to 1970s, and thereafter it declined into the early 2000s. Using 7-year-olds as an example, underweight changed from 10% to 7% in girls and from 9% to 6% in boys during the study period. The prevalence of overweight plateaued from 1950 to 1970s and then steeply increased from 1970s onwards and in 1990-2000s 15% girls and 11% boys at 7 years had overweight. The prevalence of obesity particularly increased from 1980s onwards and in 1990-2000s 5% girls and 4% boys at 7 years had obesity. These trends slightly differed by age. CONCLUSION: Among Danish schoolchildren, the prevalence of underweight was greater than overweight until the 1980s and greater than obesity throughout the period. Thus, monitoring the prevalence of childhood underweight remains an important public health issue.

Time to pregnancy and life expectancy: a cohort study of 18 796 pregnant couples.

STUDY QUESTION: Is fecundity, measured as time to pregnancy (TTP), associated with mortality in parents? SUMMARY ANSWER: Prolonged TTP is associated with increased mortality in both mothers and fathers in a dose-response manner. WHAT IS KNOWN ALREADY: Several studies have linked both male and female fecundity to mortality. In women, infertility has been linked to several diseases, but studies suggest that the underlying conditions, rather than infertility, increase mortality. STUDY DESIGN, SIZE, DURATION: A prospective cohort study was carried out on 18 796 pregnant couples, in which the pregnant women attended prophylactic antenatal care between 1973 and 1987 at a primary and tertiary care unit. The couples were followed in Danish mortality registers from their child's birth date until death or until 2018. The follow-up period was up to 47 years, and there was complete follow-up until death, emigration or end of study. PARTICIPANTS/MATERIALS, SETTING, METHODS: At the first antenatal visit, the pregnant women were asked to report the time to the current pregnancy. Inclusion was restricted to the first pregnancy, and TTP was categorised into <12 months, ≥12 months, not planned, and not available. In sub-analyses, TTP ≥12 was further categorized into 12-35, 36-60, and >60 months. Information for parents was linked to several Danish nationwide health registries. Survival analysis was used to estimate the hazard ratios (HRs) with a 95% CI for survival and adjusted for age at the first attempt to become pregnant, year of birth, socioeconomic status, mother's smoking during pregnancy, and mother's BMI. MAIN RESULTS AND THE ROLE OF CHANCE: Mothers and fathers with TTP >60 months survived, respectively, 3.5 (95% CI: 2.6-4.3) and 2.7 (95% CI: 1.8-3.7) years shorter than parents with a TTP <12 months. The mortality was higher for fathers (HR: 1.21, 95% CI: 1.09-1.34) and mothers (HR: 1.29, 95% CI: 1.12-1.49) with TTP ≥12 months compared to parents with TTP <12 months. The risk of all-cause mortality during the study period increased in a dose-response manner with the highest adjusted HR of 1.98 (95% CI: 1.62-2.41) for fathers and 2.03 (95% CI: 1.56-2.63) for mothers with TTP >60 months. Prolonged TTP was associated with several different causes of death in both fathers and mothers, indicating that the underlying causes of the relation between fecundity and survival may be multi-factorial. LIMITATIONS, REASONS FOR CAUTION: A limitation is that fecundity is measured using a pregnancy-based approach. Thus, the cohort is conditioned on fertility success and excludes sterile couples, unsuccessful attempts and spontaneous abortions. The question used to measure TTP when the pregnant woman was interviewed at her first attended prophylactic antenatal care: 'From the time you wanted a pregnancy until it occurred, how much time passed?' could potentially have led to serious misclassification if the woman did not answer on time starting unprotected intercourse but on the start of wishing to have a child. WIDER IMPLICATIONS OF THE FINDINGS: We found that TTP is a strong marker of survival, contributing to the still-emerging evidence that fecundity in men and women reflects their health and survival potential. STUDY FUNDING/COMPETING INTEREST(S): The authors acknowledge an unrestricted grant from Ferring. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication. M.L.E. is an advisor to Ro, VSeat, Doveras, and Next. TRIAL REGISTRATION NUMBER: N/A.

Minute-scale oscillatory sequences in medial entorhinal cortex.

The medial entorhinal cortex (MEC) hosts many of the brain's circuit elements for spatial navigation and episodic memory, operations that require neural activity to be organized across long durations of experience1. Whereas location is known to be encoded by spatially tuned cell types in this brain region2,3, little is known about how the activity of entorhinal cells is tied together over time at behaviourally relevant time scales, in the second-to-minute regime. Here we show that MEC neuronal activity has the capacity to be organized into ultraslow oscillations, with periods ranging from tens of seconds to minutes. During these oscillations, the activity is further organized into periodic sequences. Oscillatory sequences manifested while mice ran at free pace on a rotating wheel in darkness, with no change in location or running direction and no scheduled rewards. The sequences involved nearly the entire cell population, and transcended epochs of immobility. Similar sequences were not observed in neighbouring parasubiculum or in visual cortex. Ultraslow oscillatory sequences in MEC may have the potential to couple neurons and circuits across extended time scales and serve as a template for new sequence formation during navigation and episodic memory formation.

Improving the Quality of Publications in and Advancing the Paradigms of Clinical and Social Pharmacy Practice Research: The Granada Statements / Mejorando la calidad de las publicaciones y avanzando en todos los paradigmas de la investigación de la farmacia asistencial, clínica y social: las declaraciones de Granada

Pharmacy and pharmaceutical sciences embrace a series of different disciplines. Pharmacy practice has been defined as “the scientific discipline that studies the different aspects of the practice of pharmacy and its impact on health care systems, medicine use, and patient care”. Thus, pharmacy practice studies embrace both clinical pharmacy and social pharmacy elements. Like any other scientific discipline, clinical and social pharmacy practice disseminates research findings using scientific journals. Clinical pharmacy and social pharmacy journal editors have a role in promoting the discipline by enhancing the quality of the articles published. As has occurred in other health care areas (i.e., medicine and nursing), a group of clinical and social pharmacy practice journal editors gathered in Granada, Spain to discuss how journals could contribute to strengthening pharmacy practice as a discipline. The result of that meeting was compiled in these Granada Statements, which comprise 18 recommendations gathered into six topics: the appropriate use of terminology, impactful abstracts, the required peer reviews, journal scattering, more effective and wiser use of journal and article performance metrics, and authors’ selection of the most appropriate pharmacy practice journal to submit their work (AU)

All-viral tracing of monosynaptic inputs to single birthdate-defined neurons in the intact brain.

Neuronal firing patterns are the result of inputs converging onto single cells. Identifying these inputs, anatomically and functionally, is essential to understand how neurons integrate information. Single-cell electroporation of helper genes and subsequent local injection of recombinant rabies viruses enable precise mapping of inputs to individual cells in superficial layers of the intact cortex. However, access to neurons in deeper structures requires more invasive procedures, including removal of overlying tissue. We developed a method that, through a combination of virus injections, allows us to target 4 or fewer hippocampal cells 48% of the time and a single cell 16% of the time in wild-type mice without use of electroporation or tissue aspiration. We identify local and distant monosynaptic inputs that can be functionally characterized in vivo. By expanding the toolbox for monosynaptic circuit tracing, this method will help further our understanding of neuronal integration at the level of single cells.

Functional network topography of the medial entorhinal cortex.

The medial entorhinal cortex (MEC) creates a map of local space, based on the firing patterns of grid, head-direction (HD), border, and object-vector (OV) cells. How these cell types are organized anatomically is debated. In-depth analysis of this question requires collection of precise anatomical and activity data across large populations of neurons during unrestrained behavior, which neither electrophysiological nor previous imaging methods fully afford. Here, we examined the topographic arrangement of spatially modulated neurons in the superficial layers of MEC and adjacent parasubiculum using miniaturized, portable two-photon microscopes, which allow mice to roam freely in open fields. Grid cells exhibited low levels of co-occurrence with OV cells and clustered anatomically, while border, HD, and OV cells tended to intermingle. These data suggest that grid cell networks might be largely distinct from those of border, HD, and OV cells and that grid cells exhibit strong coupling among themselves but weaker links to other cell types.

Predictors of Poor Functional Status in Adult Fontan Patients Living at Moderate Altitude.

Patients who have undergone Fontan palliation have reduced exercise tolerance measured by maximal oxygen consumption (VO2 max). Declining exercise capacity is associated with increased morbidity and mortality. The impact of hemodynamics and other variables on this population's functional status is not well understood. This study sought to identify variables that predict low VO2 max in Fontan patients living at moderate altitude (5,000-8,000 feet). We performed a retrospective cohort study of 44 adult Fontan patients living at moderate altitude who had undergone cardiopulmonary exercise testing (CPET) and cardiac catheterization. We evaluated hemodynamic parameters measured during catheterization, imaging results, and laboratory studies for correlation with VO2 max measured during CPET. Our study cohort (median age 30 years, 52% female) had exercise impairment with mean VO2 max of 21.6 mL/kg/min. Higher trans-pulmonary gradient (TPG) (p < 0.001) and mean pulmonary artery (PA) pressure (p = 0.013) were predictors of lower maximal and submaximal VO2. Higher BNP values correlated with lower VO2 max (p = 0.01). Platelet count, GGT, albumin, and pulmonary vasodilator therapy did not correlate with VO2 max. None of the studied variables were associated with higher minute ventilation to peak carbon dioxide production (VE/VCO2 slope) or change in VO2 max over time. In conclusion, higher TPG and mean PA pressure predicted lower exercise tolerance amongst our cohort of adult Fontan patients living at moderate altitude. Future studies are needed to determine if these clinical variables represent viable therapeutic targets that could result in improved exercise tolerance and outcomes in patients with Fontan circulation.

Impaired fecundity as a marker of health and survival: a Danish twin cohort study.

STUDY QUESTION: Is fecundity, measured as self-reported time to first pregnancy (TTP), a marker for subsequent health and survival? SUMMARY ANSWER: Long TTP was a marker for increased mortality among women and higher hospitalization rates for both women and men. WHAT IS KNOWN ALREADY: Poor semen quality has been linked to increased mortality and morbidity from a wide range of diseases. Associations among fecundity, health and survival among women are still uncertain and studies on actual measures of fecundity and health outcomes are rare. STUDY DESIGN, SIZE, DURATION: We performed a prospective cohort study of 7825 women and 6279 men, aged 18 and above with measures on first TTP, who participated in one of the Danish nation-wide twin surveys in 1994 (twins born 1953-1976) and 1998 (twins born 1931-1952). They were followed-up for mortality and hospital admissions from the interview until 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: Twins were identified in the Danish Twin Registry and linked to Danish registers. TTP was restricted to the first pregnancy as a categorical outcome with cut-off points at 2, 10 and 18 months. We analysed the association between TTP and survival using a Cox proportional hazards model estimating hazards ratios (HRs) with 95% confidence intervals (CIs). Fine-Gray survival models were used to estimate sub-hazard ratios for specific causes of death allowing for competing risks. Using negative binomial regression, we estimated incidence rate ratios (IRRs) with 95% CIs for all-cause and cause-specific hospitalizations. All analyses were stratified by sex and adjusted for age at interview, birth cohorts, age at first attempt to become pregnant, smoking, years in school and BMI. MAIN RESULTS AND THE ROLE OF CHANCE: In the total study population, 49.9% of women and 52.7% of men reported a TTP of less than 2 months, 30.8% of women and 29.6% of men reported a TTP of 2-9 months, 6.6% of women and 5.7% of men reported a TTP of 10-17 months, and 13.3% of women and 12.0% of men reported a TTP of 18 months or more. Among 1305 deaths, we found a higher mortality for women (HR = 1.46; 95% CI 1.15, 1.87) with a TTP of ≥18 months relative to those with a TTP of <2 months, while the highest mortality was indicated for men with a TTP of 10-17 months (HR = 1.31; 95% CI 0.98, 1.74). Among 53 799 hospitalizations, we found an increased hospitalization rate among women (HR = 1.21; 95% CI 1.0-1.41) and men (HR = 1.16; 95% CI 1.00-1.35) with a TTP of ≥18 months, and for men with a TTP of 2-9 months (HR = 1.14; 95% CI 1.01-1.30). A dose-response relationship was found for women regarding both mortality (P = 0.022) and hospitalizations (P = 0.018). Impaired fecundity was associated with a wide range of diseases and some causes of death, indicating a multi-factorial causal influence on fecundity, especially among women. LIMITATIONS, REASONS FOR CAUTION: A major limitation was that fecundity depends on both partners, which was not considered in this study. Moreover, we could not obtain information on a number of potential confounders. WIDER IMPLICATIONS OF THE FINDINGS: Fecundity seems positively correlated with overall health and may be a universal marker of future health and survival. These results add knowledge to the limited findings showing that reduced fecundity in women and poor semen quality in men may reflect worse health and a shorter life, particularly among women. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by NIH grant HD096468 (M.L.E., T.K.J. and R.L.J.). The authors declare that they have no competing interests. TRIAL REGISTRATION NUMBER: N/A.

The Ups and Downs of Firing Rate Homeostasis.

Torrado Pacheco et al. demonstrate that downward firing rate homeostasis occurs when cellular activity levels increase beyond baseline, but only during sleep-dense periods. In contrast, Hebbian-facilitated changes in firing rate occur independently of sleep and wake states.

Paternal prescription medication before conception: A retrospective cohort study of all births in Denmark 1997-2017.

AIM: To study what medication fathers are being prescribed in the months preceding conception. METHODS: A retrospective cohort study of Danish national registries, comprising all births in Denmark 1997-2017 (1.3 million births). Time trends and absolute levels of paternal prescription medication in the 6 months prior to conception were assessed. While all medications were examined (N = 1335), we focused on the main medication groups, medications that have increased in use over time, and medications for which previous evidence exists of an effect on sperm quality. RESULTS: The average number of prescriptions increased over the study period (from 0.75 prescriptions to 0.82 per birth). Polypharmacy (three or more prescriptions) increased from less than 8% to 10% of fathers. The use of pain medication, proton-pump inhibitors, selective serotonin reuptake inhibitors and some inhalants have all increased markedly over the last 20 years. CONCLUSIONS: Potential harm to the offspring done by paternal medication may present an increasing problem. As paternal medication exposure is increasing, examination of generational effects, such as major birth defects, is necessary.

Processed meat intake and incidence of colorectal cancer: a systematic review and meta-analysis of prospective observational studies.

The objective was to use accumulated evidence to explore the association between processed meat intake and risk of colorectal cancer (CRC) and to investigate the reliability of associations by evaluating patterns of risk by study population characteristics and research quality parameters. We included 29 observational prospective cohort studies with relative risk estimates and 95% confidence intervals for CRC according to various levels of processed meat consumption. Risk of bias was assessed using Risk Of Bias In Non-randomized Studies-of Interventions (ROBINS-I) tool. Data sources were PubMed and Embase up to January 2017. The summary relative risks for high versus low processed meat consumption and risk of CRC, colon, and rectal cancer were 1.13 (95% CI: 1.01, 1.26), 1.19 (95% CI: 1.09, 1.31), and 1.21 (95% CI: 0.98, 1.49), respectively. Similar estimates were observed for the dose-response analyses. Heterogeneity across studies was detected in most analytical models. The overall judgment showed that two out of 29 studies had a moderate risk of bias, 25 had a serious risk of bias, and 2 had a critical risk of bias. The bias domains most often rated critical were bias due to risk of confounding, bias due to missing data, and selective outcome reporting bias. Although this meta-analysis indicates a modest association between processed meat intake and an increased risk of CRC, our assessment of internal validity warrants a cautious interpretation of these results, as most of the included studies were judged to have serious or critical risks of bias.

The economic burden of adult attention deficit hyperactivity disorder: A sibling comparison cost analysis.

AIM: Attention Deficit Hyperactivity Disorder (ADHD) is a lifespan disorder associated with considerable economic cost. While the economic burden of ADHD has been widely estimated, there is considerable variation in reported costs between studies, which typically focus on health outcomes only, lack adequate control and fail to correct for the influence of genetic and shared environmental factors. The aim of this study is to overcome these limitations to reach a fuller understanding of the economic burden of ADHD. METHOD: Using the Danish National Registers 5269 adults with a diagnosis of ADHD in adulthood who had not received a diagnosis in childhood were identified. Excluding cases with missing data, comorbid diagnoses, and cases without a same sex sibling free of any diagnosed psychiatric diagnoses, a final cohort was formed consisting of 460 sibling dyads. Using a cross-sectional method focusing on the year 2010, cost differences between each adult with ADHD and their sibling were calculated from data retrieved from health, education, crime, employment and social care registers. RESULTS: Adults with ADHD had considerably lower disposable income and paid less tax than their siblings. They also received more state benefits, had higher costs for health, social care, and crime than their siblings. The total average costs difference for the year 2010 was 20,134 euros more than their sibling for each adult with ADHD. CONCLUSION: ADHD is associated with considerable costs which are borne by both the individual and the state and underlines the need to consider the wider economic impact of ADHD beyond income and healthcare utilisation costs.

Prevalence of nocturia and fecal and urinary incontinence and the association to childhood obesity: a study of 6803 Danish school children.

INTRODUCTION: Fecal and urinary incontinence are common disorders in children. Obesity and its associated comorbidities have become increasingly common, and a relation between obesity, nocturia, incontinence, and nocturnal enuresis has been suggested. OBJECTIVE: This large scale population study aims to determine the prevalence of fecal incontinence (FI), daytime urinary incontinence (DUI), nocturnal enuresis (NE), and nocturia in children at school entry and in adolescence and to clarify whether obesity is associated to any of the aforementioned symptoms. STUDY DESIGN: First-grade children and their parents and adolescents in the seventh to ninth grades were interviewed in relation to school nurse visits. The interview included questions on whether incontinence or nocturia were experienced at least once per month. The participants' age was recorded, and weight and height were measured. Body mass index (BMI) was calculated and age standardized by the use of BMI-standard deviation score (SDS), with reference to World Health Organization normative BMI data. Obesity was defined as BMI-SDS >2. Associations between obesity and incontinence and nocturia were quantified by odds ratio (OR). RESULTS: Completed interview questionnaires and measurements were obtained from 4002 children (95.1%) in the child population and 2801 adolescents (84.4%) in the adolescent population. The mean age of children was 6.45 ± 0.39 years, and 4.4% were obese. Overall 11.2% reported FI, 21.8% DUI, 16.8% NE, and 31.4% experienced nocturia. Obesity was associated with FI in first-grade boys (OR 1.86 compared with normal weight). Mean age of adolescents was 13.9 ± 0.85 years, and 7.6% of adolescent boys and 5.5% of the girls were obese. Fecal incontinence was reported by 2.1% of the adolescents, 4.5% had DUI, 1.0% stated to have NE, and 32.3% reported nocturia. Obesity was significantly associated with nocturia in adolescents (OR 1.74-2.01). DISCUSSION: The prevalence of nocturia seems constant throughout childhood and adolescent life; this has not previously been documented. Incontinence is very common at school entry, with DUI reported more frequently than enuresis by both children and adolescents. Obesity is associated with nocturia in adolescents and FI in first-grade boys, but no significant association between obesity and NE or DUI is found. Strength of this study is the very high participation rates, but the study does not reveal information on previous treatment, subtype, or severity of symptoms. CONCLUSIONS: Incontinence is very common in children. One-third of both children and adolescents experience nocturia. Obesity is associated with FI in first-grade boys and nocturia in adolescents.

Results of a Search for Sub-GeV Dark Matter Using 2013 LUX Data.

The scattering of dark matter (DM) particles with sub-GeV masses off nuclei is difficult to detect using liquid xenon-based DM search instruments because the energy transfer during nuclear recoils is smaller than the typical detector threshold. However, the tree-level DM-nucleus scattering diagram can be accompanied by simultaneous emission of a bremsstrahlung photon or a so-called "Migdal" electron. These provide an electron recoil component to the experimental signature at higher energies than the corresponding nuclear recoil. The presence of this signature allows liquid xenon detectors to use both the scintillation and the ionization signals in the analysis where the nuclear recoil signal would not be otherwise visible. We report constraints on spin-independent DM-nucleon scattering for DM particles with masses of 0.4-5 GeV/c^{2} using 1.4×10^{4} kg day of search exposure from the 2013 data from the Large Underground Xenon (LUX) experiment for four different classes of mediators. This analysis extends the reach of liquid xenon-based DM search instruments to lower DM masses than has been achieved previously.

Religiousness and Diseases in Europe: Findings from SHARE.

Recent research in religiousness and health suggests that epidemiological forces can have opposed effects. Here we examine two forms of religiousness and their association with disease. We performed a cross-sectional study of 23,864 people aged 50+ included in wave 1 (2004-2005) of the Survey of Health, Ageing and Retirement in Europe and a longitudinal study including people from wave 1, who were followed up during 11 years. Results suggested that taking part in a religious organization was associated with lower odds of heart attack (OR 0.74, 95% CI 0.60, 0.90), stroke (OR 0.68, 95% CI 0.50, 0.95), and diabetes (OR 0.72, 95% CI 0.58, 0.90) and longitudinally associated with lower odds of cancer (OR 0.78, 95% CI 0.60, 1.00). Conversely, praying was longitudinally associated with higher odds of heart attack (OR 1.27, 95% CI 1.10, 1.48) and high cholesterol (OR 1.12, 95% CI 1.00, 1.26). The most religious people had lower odds of stroke, diabetes, and cancer than other respondents, and in the longitudinal model, people who only prayed had higher odds of heart attack than non-religious people. Our findings lend support to the hypothesis that restful religiousness (praying, taking part in a religious organization, and being religiously educated) was associated with lower odds of some diseases, whereas little evidence was present that crisis religiousness (praying only) was associated with higher odds of disease.

Religiousness and lifestyle among Europeans in SHARE.

OBJECTIVES: Religiousness is associated with longevity and better physical health, which may be due to lifestyle choices. Here, we examine associations between religiousness and health, explained by lifestyle. STUDY DESIGN: This is a longitudinal study. METHODS: Data came from 23,864 people aged 50 and above included in the Survey of Health, Ageing and Retirement in Europe in 2004-2005 and followed up during 11 years. RESULTS: Praying and taking part in a religious organization were associated with lower odds of smoking [odds ratio (OR) = 0.82, 95% confidence interval (CI): 0.73, 0.92 and 0.61, 95% CI: 0.53, 0.70], alcohol consumption (OR = 0.71, 95% CI: 0.64, 0.78 and OR = 0.76, 95% CI: 0.67, 0.85), physical inactivity (OR = 0.88, 95% CI: 0.79, 0.98 and OR = 0.54, 95% CI: 0.48, 0.61), and doing no vigorous physical activity (OR = 0.92, 95% CI: 0.85, 0.98 and OR = 0.63, 95% CI: 0.58, 0.68). Furthermore, religious organizational involvement lowered the odds of sleep problems (OR = 0.83, 95% CI: 0.76, 0.91), whereas being religiously educated lowered the odds of high body weight (OR = 0.87, 95% CI: 0.79, 0.96). The more religious (people who prayed, took part in a religious organization and were religiously educated) had lower odds of smoking, alcohol consumption, physical inactivity, and sleep problems than other respondents, and compared with people who only prayed, they had lower odds of smoking, physical inactivity, and sleep problems. People who only prayed had lower odds of alcohol consumption but higher odds of sleep problems than the non-religious. CONCLUSIONS: This study confirms that the positive relations between religiousness and health to an important degree can be explained by lifestyle.

Semen quality associated with subsequent hospitalizations - Can the effect be explained by socio-economic status and lifestyle factors?

Semen quality is suggested to be a universal biomarker for future health. Previous studies have mostly been registry based excluding the possibility to address the importance of lifestyle, fertility status, health and socio-economic status. We aimed to investigate whether the association between semen quality and subsequent risk of hospitalization could be explained by differences in occupation, education, fertility, cryptorchidism, BMI or smoking; 1423 men with first semen sample at Fertility Clinic, Frederiksberg Hospital, Denmark, from 1977 to 2010 responded to a questionnaire in 2012 about current health, lifestyle, educational level and occupation. They were followed in the Danish National Patient Registry to first-time hospitalizations using ICD-8 and ICD-10 classification. Data were analysed by Cox proportional hazard regression models to adjust for the possible confounding factors. We found a significant higher risk of being hospitalized with decreasing sperm concentrations (0-15 mill/mL: HR1.78, 95% CI:1.51-2.09; 16-50 mill/mL: HR 1.37 95% CI: 1.17-1.60; 51-100 mill/mL: HR1.25 95% CI: 1.07-1.45). Same significant association of being hospitalized with decreasing total sperm counts was seen. The dose-response increase in risk in hospitalization with decreasing sperm concentration and total sperm count remained constant after further individual adjustment for occupation, marital status, fertility, cryptorchidism, BMI or smoking. The association between semen quality and subsequent morbidity was not explained by differences in lifestyle, behavioural or fertility status. We were unable to adjust for all possible confounders simultaneously due to limited sample size, and reverse causation is a possible explanation as information about education and lifestyle was obtained after semen analysis and hospitalizations occurred and may have changed as consequence of both. Semen quality may be a universal biomarker for future health not explained by lifestyle and socio-economic status, but this needs to be addressed further in future studies.

Increasing the quantity of separated post-consumer plastics for reducing combustible household waste: The case of rigid plastics in Flanders.

In Flanders, Belgium, rigid and soft plastics represent an interesting fraction of residual household waste as a potential 80 000 Gg a-1 can be recycled instead of incinerated. Removing a large amount of rigid packaging and non-packaging plastics from the residual household waste fraction could contribute to the goal to reduce the amount of residual household waste to less than 150 kg capita-1 a-1 for the Flemish region, where currently only 20% of plastics are collected selectively in drop-off facilities. Given the wide range of plastic separation schemes across the region, it is the aim of this paper to identify whether the applied separation options have an impact on the quantity of separated plastics, and, moreover, which scheme is able to separate most plastics. Cross-sectional data for the period 2008-2012 were collected for all 308 Flemish municipalities to conduct a regression analysis. The results of the analysis show that the quantity of separated plastics differs significantly between the different separation schemes used. If municipalities change their separation schemes, Flanders as a whole would be able to collect more plastic waste to better comply with its own objectives and EU regulation on recycling. Improved separation-at-source recycling initiatives, by applying the appropriate separation scheme for plastics, may increase recycling growth.

Estimating the causal effect of body mass index on hay fever, asthma and lung function using Mendelian randomization.

BACKGROUND: Observational studies have shown that body mass index (BMI) is positively associated with asthma. However, observational data are prone to confounding and reverse causation. In Mendelian randomization, genetic variants are used as unconfounded markers of exposures to examine causal effects. We examined the causal effect of BMI on asthma, hay fever, allergic sensitization, serum total immunoglobulin E (IgE), forced expiratory volume in one-second (FEV1) and forced vital capacity (FVC). METHODS: We included 490 497 participants in the observational and 162 124 participants in the genetic analyses. A genetic risk score (GRS) was created using 26 BMI-associated single nucleotide polymorphisms (SNPs). Results were pooled in meta-analyses and expressed as odds ratios (ORs) or ß-estimates with 95% confidence interval (CI). RESULTS: The GRS was significantly associated with asthma (OR=1.009; 95% CI: 1.004, 1.013), but not with hay fever (OR= 0.998; 95% CI: 0.994, 1.002) or allergic sensitization (OR=0.999; 95% CI: 0.986, 1.012) per BMI-increasing allele. The GRS was significantly associated with decrease in FEV1: ß=-0.0012 (95% CI: -0.0019, -0.0006) and FVC: ß=-0.0022 (95% CI: -0.0031, -0.0014) per BMI-increasing allele. Effect sizes estimated by instrumental variable analyses were OR=1.07 (95% CI: 1.03, 1.10) for asthma, a 9 ml decrease in FEV1 (95% CI: 2.0-15 mL decrease) and a 16 ml decrease in FVC (95% CI: 7.0-24 mL decrease) per 1 kg/m2 higher BMI. CONCLUSIONS: The results support the conclusion that increasing BMI is causally related to higher prevalence of asthma and decreased lung function, but not with hay fever or biomarkers of allergy.

Deprivation-Induced Homeostatic Spine Scaling In Vivo Is Localized to Dendritic Branches that Have Undergone Recent Spine Loss.

Synaptic scaling is a key homeostatic plasticity mechanism and is thought to be involved in the regulation of cortical activity levels. Here we investigated the spatial scale of homeostatic changes in spine size following sensory deprivation in a subset of inhibitory (layer 2/3 GAD65-positive) and excitatory (layer 5 Thy1-positive) neurons in mouse visual cortex. Using repeated in vivo two-photon imaging, we find that increases in spine size are tumor necrosis factor alpha (TNF-α) dependent and thus are likely associated with synaptic scaling. Rather than occurring at all spines, the observed increases in spine size are spatially localized to a subset of dendritic branches and are correlated with the degree of recent local spine loss within that branch. Using simulations, we show that such a compartmentalized form of synaptic scaling has computational benefits over cell-wide scaling for information processing within the cell.