Estimated number of symptomatic Lyme borreliosis cases in Germany in 2021 after adjusting for under-ascertainment.

BACKGROUND: Although nine of 16 federal states in Germany conduct public health surveillance for Lyme borreliosis (LB), the extent of under-ascertainment is unknown. OBJECTIVE: As a model for European countries that conduct LB surveillance, we sought to estimate the population-based incidence of symptomatic LB after adjusting for under-ascertainment. METHODS: Estimating seroprevalence-derived under-ascertainment relies on data from seroprevalence studies, public health surveillance, and published literature. The number of symptomatic LB cases in states that conduct LB surveillance was estimated from studies reporting the seroprevalence of antibodies against Borrelia burgdorferi sensu lato, the proportion of LB cases that are asymptomatic, and the duration of antibody detection. The number of estimated incident symptomatic LB cases was compared with the number of surveillance-reported LB cases to derive under-ascertainment multipliers. The multipliers were applied to the number of 2021 surveillance-reported LB cases to estimate the population-based incidence of symptomatic LB in Germany. RESULTS: Adjusting for seroprevalence-based under-ascertainment multipliers, the estimated number of symptomatic LB cases in states that conducted surveillance was 129,870 (408 per 100,000 population) in 2021. As there were 11,051 surveillance-reported cases in 2021 in these states, these data indicate there were 12 symptomatic LB cases for every surveillance-reported LB case. CONCLUSIONS: We demonstrate that symptomatic LB is underdetected in Germany and that this seroprevalence-based approach can be applied elsewhere in Europe where requisite data are available. Nationwide expansion of LB surveillance would further elucidate the true LB disease burden in Germany and could support targeted disease prevention efforts to address the high LB disease burden.

Societal importance of Antarctic negative feedbacks on climate change: blue carbon gains from sea ice, ice shelf and glacier losses.

Diminishing prospects for environmental preservation under climate change are intensifying efforts to boost capture, storage and sequestration (long-term burial) of carbon. However, as Earth's biological carbon sinks also shrink, remediation has become a key part of the narrative for terrestrial ecosystems. In contrast, blue carbon on polar continental shelves have stronger pathways to sequestration and have increased with climate-forced marine ice losses-becoming the largest known natural negative feedback on climate change. Here we explore the size and complex dynamics of blue carbon gains with spatiotemporal changes in sea ice (60-100 MtCyear-1), ice shelves (4-40 MtCyear-1 = giant iceberg generation) and glacier retreat (< 1 MtCyear-1). Estimates suggest that, amongst these, reduced duration of seasonal sea ice is most important. Decreasing sea ice extent drives longer (not necessarily larger biomass) smaller cell-sized phytoplankton blooms, increasing growth of many primary consumers and benthic carbon storage-where sequestration chances are maximal. However, sea ice losses also create positive feedbacks in shallow waters through increased iceberg movement and scouring of benthos. Unlike loss of sea ice, which enhances existing sinks, ice shelf losses generate brand new carbon sinks both where giant icebergs were, and in their wake. These also generate small positive feedbacks from scouring, minimised by repeat scouring at biodiversity hotspots. Blue carbon change from glacier retreat has been least well quantified, and although emerging fjords are small areas, they have high storage-sequestration conversion efficiencies, whilst blue carbon in polar waters faces many diverse and complex stressors. The identity of these are known (e.g. fishing, warming, ocean acidification, non-indigenous species and plastic pollution) but not their magnitude of impact. In order to mediate multiple stressors, research should focus on wider verification of blue carbon gains, projecting future change, and the broader environmental and economic benefits to safeguard blue carbon ecosystems through law.

Comparison of pneumococcal vaccination response in children with sickle cell disease: HbSS and HbSC.

INTRODUCTION: Sickle cell disease (SCD) children are at increased risk of invasive pneumococcal disease and rely on penicillin prophylaxis and vaccination for infection prevention. Post-vaccination antibody levels in SCD may wane overtime. HbSC are believed to have better immunological response than HbSS. OBJECTIVE: To compare antibody response to 23-valent pneumococcal polysaccharide vaccine (PPSV-23) between HbSS and HbSC. METHODS: Patients with HbSS (n=33) and HbSC (n=11), aged 7-18 years, were prospectively recruited. Luminex pneumococcal antibody levels were measured for 23-serotypes, after two PPSV-23 doses. RESULTS: Absolute median titer for 20 of the 23 serotypes was higher in HbSC than HbSS and significantly higher for serotypes 22 (3.9 vs. 1.6mcg/ml; p=0.039) and 43 (2.9 vs. 0.8mcg/ml; p=0.007). HbSC mounted a better immune anti-pneumococcal response compared to HbSS (≥1.3mcg/ml) for 18 of 23 serotypes, albeit not significant for any of the serotypes. More HbSC (64%) than HbSS (42%) were good vaccine responders (p=0.303). Two of 21 (10%) good vaccine responders and nine of 23 (39%) poor vaccine responders SCD participants subsequently developed acute chest syndrome or pneumonia (p=0.036). None of the HbSC patients developed ACS after receiving PPSV-23. HbSS poor vaccine responders were at increased future recurrence risk for ACS (p=0.003), pneumonia (p=0.036) or both (p=0.011), compared to good vaccine responders. CONCLUSION: HbSC possess better pneumococcal vaccine response than HbSS. Poor vaccine response is concerning for future acute pulmonary events. Current vaccination strategy for SCD sub-types are lacking, therefore further study to evaluate utility of vaccine boosters is necessary.

Pesticide-Induced Stress in Arthropod Pests for Optimized Integrated Pest Management Programs.

More than six decades after the onset of wide-scale commercial use of synthetic pesticides and more than fifty years after Rachel Carson's Silent Spring, pesticides, particularly insecticides, arguably remain the most influential pest management tool around the globe. Nevertheless, pesticide use is still a controversial issue and is at the regulatory forefront in most countries. The older generation of insecticide groups has been largely replaced by a plethora of novel molecules that exhibit improved human and environmental safety profiles. However, the use of such compounds is guided by their short-term efficacy; the indirect and subtler effects on their target species, namely arthropod pest species, have been neglected. Curiously, comprehensive risk assessments have increasingly explored effects on nontarget species, contrasting with the majority of efforts focused on the target arthropod pest species. The present review mitigates this shortcoming by hierarchically exploring within an ecotoxicology framework applied to integrated pest management the myriad effects of insecticide use on arthropod pest species.

Higher resting-state activity in reward-related brain circuits in obese versus normal-weight females independent of food intake.

BACKGROUND: In response to food cues, obese vs normal-weight individuals show greater activation in brain regions involved in the regulation of food intake under both fasted and sated conditions. Putative effects of obesity on task-independent low-frequency blood-oxygenation-level-dependent signals-that is, resting-state brain activity-in the context of food intake are, however, less well studied. OBJECTIVE: To compare eyes closed, whole-brain low-frequency BOLD signals between severely obese and normal-weight females, as assessed by functional magnetic resonance imaging (fMRI). METHODS: Fractional amplitude of low-frequency fluctuations were measured in the morning following an overnight fast in 17 obese (age: 39±11 years, body mass index (BMI): 42.3±4.8 kg m-2) and 12 normal-weight females (age: 36±12 years, BMI: 22.7±1.8 kg m-2), both before and 30 min after consumption of a standardized meal (~260 kcal). RESULTS: Compared with normal-weight controls, obese females had increased low-frequency activity in clusters located in the putamen, claustrum and insula (P<0.05). This group difference was not altered by food intake. Self-reported hunger dropped and plasma glucose concentrations increased after food intake (P<0.05); however, these changes did not differ between the BMI groups. CONCLUSION: Reward-related brain regions are more active under resting-state conditions in obese than in normal-weight females. This difference was independent of food intake under the experimental settings applied in the current study. Future studies involving males and females, as well as utilizing repeated post-prandial resting-state fMRI scans and various types of meals are needed to further investigate how food intake alters resting-state brain activity in obese humans.

Using semifield studies to examine the effects of pesticides on mobile terrestrial invertebrates.

Many farmers rely on regular pesticide applications to avoid losses from arthropod pests and the diseases they vector. However, widespread and injudicious use of pesticides is detrimental to the environment, poses a health risk, and undermines biocontrol services. Researchers are increasingly required to develop techniques to quantify the trade-offs and risks associated with pesticides. Laboratory studies, though useful for assessing short-term impacts (e.g., mortality), cannot detect longer-term or indirect effects that can potentially be assessed using semifield studies. Here we review the range and scope of studies that have used semifield methods for regulatory testing and risk assessment of pesticides and for understanding the community-level effects of pesticide use in agricultural landscapes. We include studies on target and nontarget species, with an emphasis on quantifying effects when the target species is highly mobile. We suggest improvements in the design and analysis of semifield studies to more effectively assess effects on highly mobile species.

Estimating the prevalence of hepatitis C infection in New York City using surveillance data.

Hepatitis C virus is the most common chronic blood-borne infection in the USA. Based on results of a serosurvey, national prevalence is estimated to be 1·3% or 3·2 million people. Sub-national estimates are not available for most jurisdictions. Hepatitis C surveillance data was adjusted for death, out-migration, under-diagnosis, and undetectable blood RNA, to estimate prevalence in New York City (NYC). The prevalence of hepatitis C infection in adults aged ⩾20 years in NYC is 2·37% (range 1·53-4·90%) or 146 500 cases of hepatitis C. This analysis presents a mechanism for generating prevalence estimates using local surveillance data accounting for biases and difficulty in accessing hard to reach populations. As the cohort of patients with hepatitis C age and require additional medical care, local public health officials will need a method to generate prevalence estimates to allocate resources. This approach can serve as a guideline for generating local estimates using surveillance data that is less resource prohibitive.

Germination of conidia of Aspergillus niger is accompanied by major changes in RNA profiles.

The transcriptome of conidia of Aspergillus niger was analysed during the first 8 h of germination. Dormant conidia started to grow isotropically two h after inoculation in liquid medium. Isotropic growth changed to polarised growth after 6 h, which coincided with one round of mitosis. Dormant conidia contained transcripts from 4 626 genes. The number of genes with transcripts decreased to 3 557 after 2 h of germination, after which an increase was observed with 4 780 expressed genes 8 h after inoculation. The RNA composition of dormant conidia was substantially different than all the subsequent stages of germination. The correlation coefficient between the RNA profiles of 0 h and 8 h was 0.46. They were between 0.76-0.93 when profiles of 2, 4 and 6 h were compared with that of 8 h. Dormant conidia were characterised by high levels of transcripts of genes involved in the formation of protecting components such as trehalose, mannitol, protective proteins (e.g. heat shock proteins and catalase). Transcripts belonging to the Functional Gene Categories (FunCat) protein synthesis, cell cycle and DNA processing and respiration were over-represented in the up-regulated genes at 2 h, whereas metabolism and cell cycle and DNA processing were over-represented in the up-regulated genes at 4 h. At 6 h and 8 h no functional gene classes were over- or under-represented in the differentially expressed genes. Taken together, it is concluded that the transcriptome of conidia changes dramatically during the first two h and that initiation of protein synthesis and respiration are important during early stages of germination.

The effect of natamycin on the transcriptome of conidia of Aspergillus niger.

The impact of natamycin on Aspergillus niger was analysed during the first 8 h of germination of conidia. Polarisation, germ tube formation, and mitosis were inhibited in the presence of 3 and 10 µM of the anti-fungal compound, while at 10 µM also isotropic growth was affected. Natamycin did not have an effect on the decrease of microviscosity during germination and the concomitant reduction in mannitol and trehalose levels. However, it did abolish the increase of intracellular levels of glycerol and glucose during the 8 h period of germination.Natamycin hardly affected the changes that occur in the RNA profile during the first 2 h of germination. During this time period, genes related to transcription, protein synthesis, energy and cell cycle and DNA processing were particularly up-regulated. Differential expression of 280 and 2586 genes was observed when 8 h old germlings were compared with conidia that had been exposed to 3 µM and 10 µM natamycin, respectively. For instance, genes involved in ergosterol biosynthesis were down-regulated. On the other hand, genes involved in endocytosis and the metabolism of compatible solutes, and genes encoding protective proteins were up-regulated in natamycin treated conidia.

Thermal finite element analysis of localized hypothermia treatment of the human eye.

Localized hypothermia treatment can reduce the risk of vision loss due to ocular trauma. Hypothermia reduces inflammation and metabolic rate, and improves blood flow to prevent nerve and tissue damage. This paper presents a finite element thermal analysis to determine the efficacy of local hypothermia treatment administered using a scleral eye contact ring that acts as a heat sink. A realistic model of the human eye orbit, including fat and muscle, is created using MRI scans. A simplified CAD-based model is also created based on the first model. A transient analysis is performed by lowering the contact surface between the device and the eye to 4∘C. The study shows that the device lowers the temperature of the optic nerve head to a therapeutic range of 32-34∘C in less than 10 min of treatment, hence supporting the efficacy of such a device.

Inferring biological mechanisms from spatial analysis: prediction of a local inhibitor in the ovary.

Female mammals are born with a lifetime's supply of oocytes individually enveloped in flattened epithelial cells to form primordial follicles. It is not clear how sufficient primordial follicles are maintained to sustain the reproductive lifespan, while providing an adequate supply of mature oocytes for ovulation. Locally produced growth factors are thought to be critical regulators of early follicle growth, but knowledge of their identity and source remains incomplete. Here, we have used a simple approach of spatial analysis of structures in histological tissue sections to identify likely sources of such regulatory molecules, narrowing the field for future screening for candidate growth factors or antagonists. We have quantified the relative spatial positions of primordial (resting) follicles and growing follicles in mice on days 4, 8, and 12 after birth, and calculated interfollicular distances. Follicles were significantly less likely to have started growing if they had 1 or more primordial follicles close by (within 10 mum), predicting that primordial follicles inhibit each other. This approach allows us to hypothesize that primordial follicles produce a diffusible inhibitor that prevents neighboring primordial follicles from growing. Such an approach has wide applicability within many branches of developmental and cell biology for studying spatial signaling within tissues and cells.

A wire-flooring model for inducing lameness in broilers: evaluation of probiotics as a prophylactic treatment.

Bacterial chondronecrosis with osteomyelitis (BCO) is the most common cause of lameness in commercial broilers. Bacteria entering the blood via translocation from the respiratory system or gastrointestinal tract spread hematogenously to the proximal epiphyseal-physeal cartilage of rapidly growing femora and tibiae, causing BCO. We tested the hypothesis that rearing broilers on wire flooring should increase the incidence of BCO by persistently imposing additional torque and shear stress on susceptible leg joints. We also tested the hypothesis that probiotics might attenuate bacterial translocation and thereby reduce the incidence of BCO. In 5 independent experiments using 4 commercial lines, broilers grown on wire flooring developed lameness attributable predominately to BCO. The fastest-growing birds were not necessarily the most susceptible to lameness on wire flooring, nor did the genders differ in susceptibility in the 2 experiments that included both male and female broilers. The pathogenesis of BCO is not instantaneous, and accordingly, many broilers that did not exhibit lameness, nevertheless, did possess early pathognomonic lesions. These subclinical lesions were equally likely to develop in the right or left leg. The lesion status of the proximal femoral head did not determine the lesion status of the ipsilateral or contralateral proximal tibial head and vice versa. Broilers reared on wire flooring consistently had higher incidences of lameness than hatch-mates reared on wood-shavings litter. Adding probiotics to the diet beginning at 1 d of age consistently reduced the incidence of lameness for broilers reared on wire flooring. These experiments indicate that probiotics administered prophylactically may constitute an alternative to antibiotics for reducing lameness attributable to BCO. Rearing broilers on wire flooring provides an important new research model for investigating the etiology, pathogenesis, and treatment strategies for BCO.

NNLO interpolation grids for jet production at the LHC.

Fast interpolation-grid frameworks facilitate an efficient and flexible evaluation of higher-order predictions for any choice of parton distribution functions or value of the strong coupling α s . They constitute an essential tool for the extraction of parton distribution functions and Standard Model parameters, as well as studies of the dependence of cross sections on the renormalisation and factorisation scales. The APPLfast project provides a generic interface between the parton-level Monte Carlo generator and both the APPLgrid and the fastNLO libraries for the grid interpolation. The extension of the project to include hadron-hadron collider processes at next-to-next-to-leading order in perturbative QCD is presented, together with an application for jet production at the LHC.

Standard or extended-duration prophylaxis in medical patients? A review of the evidence.

Acutely ill medical patients are at significant risk of venous thromboembolism (VTE). Thromboprophylaxis can substantially reduce the incidence of VTE, but to be optimally effective must consist of the correct choice of agent, at an appropriate dose, and for sufficient duration. Increasing evidence suggests that VTE risk persists beyond the standard period of prophylaxis. Although there is evidence that extended-duration prophylaxis is beneficial in preventing late VTE complications in high-risk surgical patients, few data exist in medical patients. The recent EXCLAIM study demonstrated that, subsequent to a standard prophylaxis regimen of 10 ± 4 days with enoxaparin 40 mg once daily, extended-duration prophylaxis (28 ± 4 days) with enoxaparin reduced total VTE events compared with placebo: 2.5% versus 4.0%; (absolute risk difference -1.53%; 95.8% confidence interval [CI] -2.54 to -0.52), with parallel increases in major bleeding rates (0.8% vs. 0.3%; absolute risk difference 0.51%; 95% CI 0.12-0.89%). The reduction in total VTE was principally driven by a decrease in symptomatic deep-vein thrombosis (absolute risk difference -0.60%; 95.8% CI -1.00 to -0.19%). Favorable benefit-to-risk ratios were observed in certain high-risk patient groups: level 1 immobility, women, and age >75 years. In addition to their underlying medical condition, medical patients often have multiple risk factors, placing them at sustained risk of VTE. Extended-duration prophylaxis might be most relevant in such patients. The development of appropriate risk assessment tools could help identify medical patients at greatest risk of late VTE events who might benefit most from extended-duration prophylaxis.

An ultralow-noise superconducting radio-frequency ion trap for frequency metrology with highly charged ions.

We present a novel ultrastable superconducting radio-frequency (RF) ion trap realized as a combination of an RF cavity and a linear Paul trap. Its RF quadrupole mode at 34.52 MHz reaches a quality factor of Q ≈ 2.3 × 105 at a temperature of 4.1 K and is used to radially confine ions in an ultralow-noise pseudopotential. This concept is expected to strongly suppress motional heating rates and related frequency shifts that limit the ultimate accuracy achieved in advanced ion traps for frequency metrology. Running with its low-vibration cryogenic cooling system, electron-beam ion trap, and deceleration beamline supplying highly charged ions (HCIs), the superconducting trap offers ideal conditions for optical frequency metrology with ionic species. We report its proof-of-principle operation as a quadrupole-mass filter with HCIs and trapping of Doppler-cooled 9Be+ Coulomb crystals.

Water- and air-distributed conidia differ in sterol content and cytoplasmic microviscosity.

Airborne and waterborne fungal spores were compared with respect to cytoplasmic viscosity and the presence of ergosterol. These parameters differed markedly between the two spore types and correlated with spore survival. This suggests that the mode of spore dispersal has a bearing on cellular composition, which is relevant for the eradication of industrially relevant fungal propagules.

Double-strand breaks and tumorigenesis.

The establishment of connections between biochemical defects and clinical disease is a major goal of modern molecular genetics. In this review, we examine the current literature that relates defects in the two major DNA double-strand-break repair pathways--homologous recombination and nonhomologous end-joining--with the development of human tumors. Although definitive proof has yet to be obtained, the current literature is highly suggestive of such a link.

Metals leaching from common residential and commercial roofing materials across four years of weathering and implications for environmental loading.

Urban stormwater is a major source of chemical pollution to receiving waters. Anthropogenic materials in the built environment can be an important source of chemicals to stormwater runoff. Roofing materials can leach significant amounts of metals, which vary over the life of the roof. We report concentrations of three metals (As, Cu, Zn) leaching into runoff from experimental panels of 14 roofing materials over 4.5 years of weathering. Ten roofing materials leached metals. Several leached >10 ppb during one or more study periods. The most common correlate with metal concentration was panel age, followed by precipitation amount. Extrapolating from these observations, we estimated the loading of metals from each roofing material during the first 10 years following installation. Eight materials were predicted to leach metals above background at the end of the 10 years. In combination with information on the prevalence of different roofing materials in the Puget Sound region of the Pacific Northwest, we estimated the relative amount of metals contributed from roofing materials in this basin. Most arsenic and copper was estimated to be contributed by residential roofing; nearly all arsenic from wood shakes manufactured with copper chromated arsenic, and copper contributed mainly from treated wood shakes followed by copper granule-containing asphalt shingles. Most zinc was estimated to be contributed by commercial roofs, including Zincalume and painted metal roofs. Overall our data shows that roofing materials can be an important long-term source of As, Cu, and Zn to stormwater runoff. Compared with atmospheric deposition, roof materials were a significant source, particularly of As and Cu. To get a complete picture of metals sourced from buildings, there is a need to study whole roof systems, including gutters, downspouts, and HVAC systems, as well as metals contributed from homeowner-applied treatments to their roofs.

Closed-cycle, low-vibration 4 K cryostat for ion traps and other applications.

In vacuo cryogenic environments are ideal for applications requiring both low temperatures and extremely low particle densities. This enables reaching long storage and coherence times, for example, in ion traps, essential requirements for experiments with highly charged ions, quantum computation, and optical clocks. We have developed a novel cryostat continuously refrigerated with a pulse-tube cryocooler and providing the lowest vibration level reported for such a closed-cycle system with 1 W cooling power for a <5 K experiment. A decoupling system suppresses vibrations from the cryocooler by three orders of magnitude down to a level of 10 nm peak amplitudes in the horizontal plane. Heat loads of about 40 W (at 45 K) and 1 W (at 4 K) are transferred from an experimental chamber, mounted on an optical table, to the cryocooler through a vacuum-insulated massive 120 kg inertial copper pendulum. The 1.4 m long pendulum allows installation of the cryocooler in a separate, acoustically isolated machine room. At the experimental chamber, we measured the residual vibrations using an interferometric setup. The positioning of the 4 K elements is reproduced to better than a few micrometer after a full thermal cycle to room temperature. Extreme high vacuum on the 10-15 mbar level is achieved. In collaboration with the Max-Planck-Institut für Kernphysik, such a setup is now in operation at the Physikalisch-Technische Bundesanstalt for a next-generation optical clock experiment using highly charged ions.