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Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) led to a significant disease burden and disruptions in health systems. We describe the epidemiology and transmission characteristics of early coronavirus disease 2019 (COVID-19) cases in Bavaria, Germany. Cases were reverse transcription polymerase chain reaction (RT-PCR)-confirmed SARS-CoV-2 infections, reported from 20 January−19 March 2020. The incubation period was estimated using travel history and date of symptom onset. To estimate the serial interval, we identified pairs of index and secondary cases. By 19 March, 3546 cases were reported. A large proportion was exposed abroad (38%), causing further local transmission. Median incubation period of 256 cases with exposure abroad was 3.8 days (95%CI: 3.5–4.2). For 95% of infected individuals, symptom onset occurred within 10.3 days (95%CI: 9.1–11.8) after exposure. The median serial interval, using 53 pairs, was 3.5 days (95%CI: 3.0–4.2; mean: 3.9, s.d.: 2.2). Travellers returning to Germany had an important influence on the spread of SARS-CoV-2 infections in Bavaria in early 2020. Especially in times of low incidence, public health agencies should identify holiday destinations, and areas with ongoing local transmission, to monitor potential importation of SARS-CoV-2 infections. Travellers returning from areas with ongoing community transmission should be advised to quarantine to prevent re-introductions of COVID-19.
To investigate the influences of dietary riboflavin (RF) addition on nutrient digestion and rumen fermentation, eight rumen cannulated Holstein bulls were randomly allocated into four treatments in a repeated 4 × 4 Latin square design. Daily addition level of RF for each bull in control, low RF, medium RF and high RF was 0, 300, 600 and 900 mg, respectively. Increasing the addition level of RF, DM intake was not affected, average daily gain tended to be increased linearly and feed conversion ratio decreased linearly. Total tract digestibilities of DM, organic matter, crude protein (CP) and neutral-detergent fibre (NDF) increased linearly. Rumen pH decreased quadratically, and total volatile fatty acids (VFA) increased quadratically. Acetate molar percentage and acetate:propionate ratio increased linearly, but propionate molar percentage and ammonia-N content decreased linearly. Rumen effective degradability of DM increased linearly, NDF increased quadratically but CP was unaltered. Activity of cellulase and populations of total bacteria, protozoa, fungi, dominant cellulolytic bacteria, Prevotella ruminicola and Ruminobacter amylophilus increased linearly. Linear increase was observed for urinary total purine derivatives excretion. The data suggested that dietary RF addition was essential for rumen microbial growth, and no further increase in performance and rumen total VFA concentration was observed when increasing RF level from 600 to 900 mg/d in dairy bulls.
Bipolar disorder is associated with premature mortality, but evidence is mostly derived from Western countries. There has been no research evaluating shortened lifespan in bipolar disorder using life-years lost (LYLs), which is a recently developed mortality metric taking into account illness onset for life expectancy estimation. The current study aimed to examine the extent of premature mortality in bipolar disorder patients relative to the general population in Hong Kong (HK) in terms of standardised mortality ratio (SMR) and excess LYLs, and changes of mortality rate over time.
This population-based cohort study investigated excess mortality in 12 556 bipolar disorder patients between 2008 and 2018, by estimating all-cause and cause-specific SMRs, and LYLs. Trends in annual SMRs over the 11-year study period were assessed. Study data were retrieved from a territory-wide medical-record database of HK public healthcare services.
Patients had higher all-cause [SMR: 2.60 (95% CI: 2.45–2.76)], natural-cause [SMR: 1.90 (95% CI: 1.76–2.05)] and unnatural-cause [SMR: 8.63 (95% CI: 7.34–10.03)] mortality rates than the general population. Respiratory diseases, cardiovascular diseases and cancers accounted for the majority of deaths. Men and women with bipolar disorder had 6.78 (95% CI: 6.00–7.84) years and 7.35 (95% CI: 6.75–8.06) years of excess LYLs, respectively. The overall mortality gap remained similar over time, albeit slightly improved in men with bipolar disorder.
Bipolar disorder is associated with increased premature mortality and substantially reduced lifespan in a predominantly Chinese population, with excess deaths mainly attributed to natural causes. Persistent mortality gap underscores an urgent need for targeted interventions to improve physical health of patients with bipolar disorder.
There is compelling evidence for gradient effects of household income on school readiness. Potential mechanisms are described, yet the growth curve trajectory of maternal mental health in a child's early life has not been thoroughly investigated. We aimed to examine the relationships between household incomes, maternal mental health trajectories from antenatal to the postnatal period, and school readiness.
Prospective data from 505 mother–child dyads in a birth cohort in Singapore were used, including household income, repeated measures of maternal mental health from pregnancy to 2-years postpartum, and a range of child behavioural, socio-emotional and cognitive outcomes from 2 to 6 years of age. Antenatal mental health and its trajectory were tested as mediators in the latent growth curve models.
Household income was a robust predictor of antenatal maternal mental health and all child outcomes. Between children from the bottom and top household income quartiles, four dimensions of school readiness skills differed by a range of 0.52 (95% Cl: 0.23, 0.67) to 1.21 s.d. (95% CI: 1.02, 1.40). Thirty-eight percent of pregnant mothers in this cohort were found to have perinatal depressive and anxiety symptoms in the subclinical and clinical ranges. Poorer school readiness skills were found in children of these mothers when compared to those of mothers with little or no symptoms. After adjustment of unmeasured confounding on the indirect effect, antenatal maternal mental health provided a robust mediating path between household income and multiple school readiness outcomes (χ2 126.05, df 63, p < 0.001; RMSEA = 0.031, CFI = 0.980, SRMR = 0.034).
Pregnant mothers with mental health symptoms, particularly those from economically-challenged households, are potential targets for intervention to level the playing field of their children.
Previous studies have revealed associations of meteorological factors with tuberculosis (TB) cases. However, few studies have examined their lag effects on TB cases. This study was aimed to analyse nonlinear lag effects of meteorological factors on the number of TB notifications in Hong Kong. Using a 22-year consecutive surveillance data in Hong Kong, we examined the association of monthly average temperature and relative humidity with temporal dynamics of the monthly number of TB notifications using a distributed lag nonlinear models combined with a Poisson regression. The relative risks (RRs) of TB notifications were >1.15 as monthly average temperatures were between 16.3 and 17.3 °C at lagged 13–15 months, reaching the peak risk of 1.18 (95% confidence interval (CI) 1.02–1.35) when it was 16.8 °C at lagged 14 months. The RRs of TB notifications were >1.05 as relative humidities of 60.0–63.6% at lagged 9–11 months expanded to 68.0–71.0% at lagged 12–17 months, reaching the highest risk of 1.06 (95% CI 1.01–1.11) when it was 69.0% at lagged 13 months. The nonlinear and delayed effects of average temperature and relative humidity on TB epidemic were identified, which may provide a practical reference for improving the TB warning system.
An acute gastroenteritis (AGE) outbreak caused by a norovirus occurred at a hospital in Shanghai, China, was studied for molecular epidemiology, host susceptibility and serological roles. Rectal and environmental swabs, paired serum samples and saliva specimens were collected. Pathogens were detected by real-time polymerase chain reaction and DNA sequencing. Histo-blood group antigens (HBGA) phenotypes of saliva samples and their binding to norovirus protruding proteins were determined by enzyme-linked immunosorbent assay. The HBGA-binding interfaces and the surrounding region were analysed by the MegAlign program of DNAstar 7.1. Twenty-seven individuals in two care units were attacked with AGE at attack rates of 9.02 and 11.68%. Eighteen (78.2%) symptomatic and five (38.4%) asymptomatic individuals were GII.6/b norovirus positive. Saliva-based HBGA phenotyping showed that all symptomatic and asymptomatic cases belonged to A, B, AB or O secretors. Only four (16.7%) out of the 24 tested serum samples showed low blockade activity against HBGA-norovirus binding at the acute phase, whereas 11 (45.8%) samples at the convalescence stage showed seroconversion of such blockade. Specific blockade antibody in the population played an essential role in this norovirus epidemic. A wide HBGA-binding spectrum of GII.6 supports a need for continuous health attention and surveillance in different settings.
Influenza vaccine effectiveness (VE) wanes over the course of a temperate climate winter season but little data are available from tropical countries with year-round influenza virus activity. In Singapore, a retrospective cohort study of adults vaccinated from 2013 to 2017 was conducted. Influenza vaccine failure was defined as hospital admission with polymerase chain reaction-confirmed influenza infection 2–49 weeks after vaccination. Relative VE was calculated by splitting the follow-up period into 8-week episodes (Lexis expansion) and the odds of influenza infection in the first 8-week period after vaccination (weeks 2–9) compared with subsequent 8-week periods using multivariable logistic regression adjusting for patient factors and influenza virus activity. Records of 19 298 influenza vaccinations were analysed with 617 (3.2%) influenza infections. Relative VE was stable for the first 26 weeks post-vaccination, but then declined for all three influenza types/subtypes to 69% at weeks 42–49 (95% confidence interval (CI) 52–92%, P = 0.011). VE declined fastest in older adults, in individuals with chronic pulmonary disease and in those who had been previously vaccinated within the last 2 years. Vaccine failure was significantly associated with a change in recommended vaccine strains between vaccination and observation period (adjusted odds ratio 1.26, 95% CI 1.06–1.50, P = 0.010).
Maternal antenatal depression strongly influences child mental health but with considerable inter-individual variation that is, in part, linked to genotype. The challenge is to effectively capture the genotypic influence. We outline a novel approach to describe genomic susceptibility to maternal antenatal depression focusing on child emotional/behavioral difficulties. Two cohorts provided measures of maternal depression, child genetic variation, and child mental health symptoms. We constructed a conventional polygenic risk score (PRS) for attention-deficit/hyperactivity disorder (ADHD) (PRSADHD) that significantly moderated the association between maternal antenatal depression and internalizing problems at 60 months (p = 2.94 × 10−4, R2 = .18). We then constructed an interaction PRS (xPRS) based on a subset of those single nucleotide polymorphisms from the PRSADHD that most accounted for the moderation of the association between maternal antenatal depression and child outcome. The interaction between maternal antenatal depression and this xPRS accounted for a larger proportion of the variance in child emotional/behavioral problems than models based on any PRSADHD (p = 5.50 × 10−9, R2 = .27), with similar findings in the replication cohort. The xPRS was significantly enriched for genes involved in neuronal development and synaptic function. Our study illustrates a novel approach to the study of genotypic moderation on the impact of maternal antenatal depression on child mental health and highlights the utility of the xPRS approach. These findings advance our understanding of individual differences in the developmental origins of mental health.
We describe here efforts to create and study magnetized electron–positron pair plasmas, the existence of which in astrophysical environments is well-established. Laboratory incarnations of such systems are becoming ever more possible due to novel approaches and techniques in plasma, beam and laser physics. Traditional magnetized plasmas studied to date, both in nature and in the laboratory, exhibit a host of different wave types, many of which are generically unstable and evolve into turbulence or violent instabilities. This complexity and the instability of these waves stem to a large degree from the difference in mass between the positively and the negatively charged species: the ions and the electrons. The mass symmetry of pair plasmas, on the other hand, results in unique behaviour, a topic that has been intensively studied theoretically and numerically for decades, but experimental studies are still in the early stages of development. A levitated dipole device is now under construction to study magnetized low-energy, short-Debye-length electron–positron plasmas; this experiment, as well as a stellarator device that is in the planning stage, will be fuelled by a reactor-based positron source and make use of state-of-the-art positron cooling and storage techniques. Relativistic pair plasmas with very different parameters will be created using pair production resulting from intense laser–matter interactions and will be confined in a high-field mirror configuration. We highlight the differences between and similarities among these approaches, and discuss the unique physics insights that can be gained by these studies.
Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.
A disruption database characterizing the current quench of disruptions with ITER-like tungsten divertor has been developed on EAST. It provides a large number of plasma parameters describing the predisruptive plasma, current quench time, eddy current, and mitigation by massive impurity injection, which shows that the current quench time strongly depends on magnetic energy and post-disruption electron temperature. Further, the energy balance and magnetic energy dissipation during the current quench phase has been well analysed. Magnetic energy is also demonstrated to be dissipated mainly by ohmic reheating and inductive coupling, and both of the two channels have great effects on current quench time. Also, massive gas injection is an efficient method to speed up the current quench and increase the fraction of impurity radiation.
Infection prevention and control (IPC) workflows are often retrospective and manual. New tools, however, have entered the field to facilitate rapid prospective monitoring of infections in hospitals. Although artificial intelligence (AI)–enabled platforms facilitate timely, on-demand integration of clinical data feeds with pathogen whole-genome sequencing (WGS), a standardized workflow to fully harness the power of such tools is lacking. We report a novel, evidence-based workflow that promotes quicker infection surveillance via AI-assisted clinical and WGS data analysis. The algorithm suggests clusters based on a combination of similar minimum inhibitory concentration (MIC) data, timing of sample collection, and shared location stays between patients. It helps to proactively guide IPC professionals during investigation of infectious outbreaks and surveillance of multidrug-resistant organisms and healthcare-acquired infections. Methods: Our team established a 1-year workgroup comprised of IPC practitioners, clinical experts, and scientists in the field. We held weekly roundtables to study lessons learned in an ongoing surveillance effort at a tertiary care hospital—utilizing Philips IntelliSpace Epidemiology (ISEpi), an AI-powered system—to understand how such a tool can enhance practice. Based on real-time case discussions and evidence from the literature, a workflow guidance tool and checklist were codified. Results: In our workflow, data-informed clusters posed by ISEpi underwent triage and expert follow-up analysis to assess: (1) likelihood of transmission(s); (2) potential vector(s) identity; (3) need to request WGS; and (4) intervention(s) to be pursued, if warranted. In a representative sample (spanning October 17, 2019, to November 7, 2019) of 67 total isolates suggested for inclusion in 19 unique cluster investigations, we determined that 9 investigations merited follow-up. Collectively, these 9 investigations involved 21 patients and required 115 minutes to review in ISEpi and an additional 70 minutes of review outside of ISEpi. After review, 6 investigations were deemed unlikely to represent a transmission; the other 3 had potential to represent transmission for which interventions would be performed. Conclusions: This study offers an important framework for adaptation of existing infection control workflow strategies to leverage the utility of rapidly integrated clinical and WGS data. This workflow can also facilitate time-sensitive decisions regarding sequencing of specific pathogens given the preponderance of available clinical data supporting investigations. In this regard, our work sets a new standard of practice: precision infection prevention (PIP). Ongoing effort is aimed at development of AI-powered capabilities for enterprise-level quality and safety improvement initiatives.
Funding: Philips Healthcare provided support for this study.
Disclosures: Alan Doty and Juan Jose Carmona report salary from Philips Healthcare.
The availability of large healthcare datasets offers the opportunity for researchers to navigate the traditional clinical and translational science research stages in a nonlinear manner. In particular, data scientists can harness the power of large healthcare datasets to bridge from preclinical discoveries (T0) directly to assessing population-level health impact (T4). A successful bridge from T0 to T4 does not bypass the other stages entirely; rather, effective team science makes a direct progression from T0 to T4 impactful by incorporating the perspectives of researchers from every stage of the clinical and translational science research spectrum. In this exemplar, we demonstrate how effective team science overcame challenges and, ultimately, ensured success when a diverse team of researchers worked together, using healthcare big data to test population-level substance use disorder (SUD) hypotheses generated from preclinical rodent studies. This project, called Advancing Substance use disorder Knowledge using Big Data (ASK Big Data), highlights the critical roles that data science expertise and effective team science play in quickly translating preclinical research into public health impact.
The Eating Assessment in Toddlers FFQ (EAT FFQ) has been shown to have good reliability and comparative validity for ranking nutrient intakes in young children. With the addition of food items (n 4), we aimed to re-assess the validity of the EAT FFQ and estimate calibration factors in a sub-sample of children (n 97) participating in the Growing Up Milk – Lite (GUMLi) randomised control trial (2015–2017). Participants completed the ninety-nine-item GUMLi EAT FFQ and record-assisted 24-h recalls (24HR) on two occasions. Energy and nutrient intakes were assessed at months 9 and 12 post-randomisation and calibration factors calculated to determine predicted estimates from the GUMLi EAT FFQ. Validity was assessed using Pearson correlation coefficients, weighted kappa (κ) and exact quartile categorisation. Calibration was calculated using linear regression models on 24HR, adjusted for sex and treatment group. Nutrient intakes were significantly correlated between the GUMLi EAT FFQ and 24HR at both time points. Energy-adjusted, de-attenuated Pearson correlations ranged from 0·3 (fibre) to 0·8 (Fe) at 9 months and from 0·3 (Ca) to 0·7 (Fe) at 12 months. Weighted κ for the quartiles ranged from 0·2 (Zn) to 0·6 (Fe) at 9 months and from 0·1 (total fat) to 0·5 (Fe) at 12 months. Exact agreement ranged from 30 to 74 %. Calibration factors predicted up to 56 % of the variation in the 24HR at 9 months and 44 % at 12 months. The GUMLi EAT FFQ remained a useful tool for ranking nutrient intakes with similar estimated validity compared with other FFQ used in children under 2 years.
Damage to the corticospinal tract (CST) from stroke leads to motor deficits. The damage can be quantified as the amount of overlap between the stroke lesion and CST (CST Injury). Previous literature has shown that the degree of motor deficits post-stroke is related to the amount of CST Injury. These studies delineate the stroke lesion from structural T1-weighted magnetic resonance imaging (MRI) scans, often acquired for research. In Canada, computed tomography (CT) is the most common imaging modality used in routine acute stroke care. In this proof-of-principle study, we determine whether CST Injury, using lesions delineated from CT scans, significantly explains the variability in motor impairment in individuals with stroke.
Thirty-seven participants with stroke were included in this study. These individuals had a CT scan within the acute stage (7 days) of their stroke and underwent motor assessments. Brain images from CT scans were registered to MRI space. We performed a stepwise regression analysis to determine the contribution of CST injury and demographic variables in explaining motor impairment variability.
Using clinically available CT scans, we found modest evidence that CST Injury explains variability in motor impairment (R2adj = 0.12, p = 0.02). None of the participant demographic variables entered the model.
We show for the first time a relationship between CST Injury and motor impairment using CT scans. Further work is required to evaluate the utility of data derived from clinical CT scans as a biomarker of stroke motor recovery.
Diet has direct and indirect effects on health through inflammation and the gut microbiome. We investigated total dietary inflammatory potential via the literature-derived index (Dietary Inflammatory Index (DII®)) with gut microbiota diversity, composition and function. In cancer-free patient volunteers initially approached at colonoscopy and healthy volunteers recruited from the medical centre community, we assessed 16S ribosomal DNA in all subjects who provided dietary assessments and stool samples (n 101) and the gut metagenome in a subset of patients with residual fasting blood samples (n 34). Associations of energy-adjusted DII scores with microbial diversity and composition were examined using linear regression, permutational multivariate ANOVA and linear discriminant analysis. Spearman correlation was used to evaluate associations of species and pathways with DII and circulating inflammatory markers. Across DII levels, α- and β-diversity did not significantly differ; however, Ruminococcus torques, Eubacterium nodatum, Acidaminococcus intestini and Clostridium leptum were more abundant in the most pro-inflammatory diet group, while Akkermansia muciniphila was enriched in the most anti-inflammatory diet group. With adjustment for age and BMI, R. torques, E. nodatum and A. intestini remained significantly associated with a more pro-inflammatory diet. In the metagenomic and fasting blood subset, A. intestini was correlated with circulating plasminogen activator inhibitor-1, a pro-inflammatory marker (rho = 0·40), but no associations remained significant upon correction for multiple testing. An index reflecting overall inflammatory potential of the diet was associated with specific microbes, but not overall diversity of the gut microbiome in our study. Findings from this preliminary study warrant further research in larger samples and prospective cohorts.
Ovarian follicle selection is a natural biological process in the pre-ovulatory hierarchy in birds that drives growing follicles to be selected within the ovulatory cycle. Follicle selection in birds is strictly regulated, involving signaling pathways mediated by dietary nutrients, gonadotrophic hormones and paracrine factors. This study aimed to test the hypothesis that dietary Ca may participate in regulating follicle selection in laying ducks through activating the signaling pathway of cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/extracellular signal-regulated kinase (ERK), possibly mediated by gonadotrophic hormones. Female ducks at 22 weeks of age were initially fed one of two Ca-deficient diets (containing 1.8% or 0.38% Ca) or a Ca-adequate control diet (containing 3.6% Ca) for 67 days (depletion period), then all birds were fed the Ca-adequate diet for an additional 67 days (repletion period). Compared with the Ca-adequate control, ducks fed 0.38% Ca during the depletion period had significantly decreased (P < 0.05) numbers of hierarchical follicles and total ovarian weight, which were accompanied by reduced egg production. Plasma concentration of FSH was decreased by the diet containing 1.8% Ca but not by that containing 0.38%. The ovarian content of cAMP was increased with the two Ca-deficient diets, and phosphorylation of PKA and ERK1/2 was increased with 0.38% dietary Ca. Transcripts of ovarian estradiol receptor 2 and luteinizing hormone receptor (LHR) were reduced in the ducks fed the two Ca-deficient diets (P < 0.05), while those of the ovarian follicle stimulating hormone receptor (FSHR) were decreased in the ducks fed 0.38% Ca. The transcript abundance of ovary gap junction proteins, A1 and A4, was reduced with the Ca-deficient diets (P < 0.05). The down-regulation of gene expression of gap junction proteins and hormone receptors, the increased cAMP content and the suppressed hierarchical follicle numbers were reversed by repletion of dietary Ca. These results indicate that dietary Ca deficiency negatively affects follicle selection of laying ducks, independent of FSH, but probably by activating cAMP/PKA/ERK1/2 signaling pathway.
Test the efficacy and perceived effectiveness of nutrition labels on children’s menus from a full-service chain restaurant in an online study.
Using a between-groups experiment, parents were randomised to view children’s menus displaying one of five children’s nutrition labelling conditions: (i) No Nutrition Information (control); (ii) Calories Only; (iii) Calories + Contextual Statement (CS); (iv) Calories, Sodium + CS; or (v) Calories and Sodium in Traffic Lights + CS. Parents hypothetically ordered up to one entrée, side, beverage and dessert for their child, then rated and ranked all five labelling conditions on the level of perceived effectiveness.
998 parents with a 3–12 year old child.
Parents exposed to menus displaying ‘Calories, Sodium + CS’ selected significantly fewer calories ‘overall’ (entrées + side + dessert + beverage) compared to parents exposed to the control condition (−53·1 calories, P < 0·05). Parents selected ‘entrees’ with significantly fewer calories and lower sodium when exposed to menus with ‘Calories + CS’ (−24·3 calories, P < 0·05); ‘Calories, Sodium + CS’ (−25·4 calories, −56·1 mg sodium, P < 0·05 for both); and ‘Calories and Sodium in Traffic Lights + CS’ (−29·1 calories, −58·6 mg sodium, P < 0·05 for both). Parents exposed to menus with ‘Calories, Sodium + CS’ and ‘Calories and Sodium in Traffic Lights + CS’ were more likely to notice and understand nutrition information compared to other nuntrition labelling conditions. Parents perceived the menu with ‘Calories and Sodium in Traffic Lights + CS’ as most effective (P < 0·05).
Menus disclosing calories, sodium and a contextual statement increased the proportion of parents who noticed and understood nutrition information, and resulted in parents selecting lower calorie and sodium entrées for their children in the hypothetical purchase task.