Alleviation of severe chronic arthritic pain using polyvalent immunoglobulins (KMP01): Two case reports.

BACKGROUND: Treatment of arthritis is carried out using corticosteroids, methotrexate, sulfasalazine-like agents, and TNF-α-blocking agents such as infliximab and adalimumab. The disadvantages of these agents are high-cost, severe side effects including leucopenia, and in some cases the necessity of administration by injection. Polyvalent immunoglobulin formulations derived from bovine colostrum and marketed as a standardized formulation for oral application, are reported to be efficacious in chronic pain syndromes but are rarely, if ever, used as an alternative medication in such patients. AIMS: To treat arthritis in a real-world setting using polyvalent immunoglobulins in 2 patients, in one case where no alternative treatment modality was available and in another patient in whom the use of polyvalent immunoglobulins appeared to be a suitable option. MATERIALS AND METHODS: Two male subjects aged 46 and 82 years with confirmed diagnosis but not well-controlled arthritis/polyarthritis receiving either high-dose NSAIDS, corticosteroids, methotrexate injections, with previous use of, or recommendations for treatment with monoclonal antibodies (etanercept and adalimumab) were treated with oral polyvalent immunoglobulins (KMP01; dose range 10 - 20 g daily) in real-world settings, in one case during a field excursion in Peru. RESULTS: The treatment produced a rapid alleviation of pain in both patients, in one patient where the symptoms were severe and debilitating. In the second patient methotrexate SC injections could be discontinued, and there was a progressive reversal of leucopenia (leucocyte count 3.9 × 103/µL) over a period of ~ 3 months. DISCUSSION: Polyvalent immunoglobulins have been shown previously to reduce the expression of interleukin-6 and C-reactive protein in peripheral blood monocytes, events attributed to the neutralization of gut-derived endotoxin ligands lipopolysaccharides (LPS) driving the basal immune response. The mode of action of KMP01 on cytokine expression is therefore similar to the TNF-α-blocking agents etanercept and adalimumab. CONCLUSION: Findings from two case reports support the rationale for using polyvalent immunoglobulins as an effective and safe alternative in arthritis patients receiving standard treatments, in particular, methotrexate and TNF-α-blocking agents.

A Heat Emergency: Urban Heat Exposure and Access to Refuge in Richmond, VA.

The urban heat island effect exacerbates independent climate change-induced shifts toward longer, stronger, and more frequent heat extremes. Environmental inequity, driven by a history of racially motivated urban planning policies, has led particular demographics to bear the worst impacts of urban heat exposure and thus also climate change. These impacts cause adverse health outcomes in the form of heat emergencies. Through a novel demographic and spatial analysis of heat-related illness Emergency Medical Services data from Richmond, Virginia, this study investigates the relationships between heat health emergencies and intra-urban heat islands quantified through three heat exposure metrics. We also evaluate the accessibility of built refuge from urban heat in the form of public transit infrastructure, libraries, and government cooling centers in relation to these emergencies. We found that heat emergencies are inequitably distributed among racial, age, and socioeconomic groups in Richmond, particularly among residents identified as Male, Black or African American, 50+ years old, and experiencing mental health, intoxication, and/or homelessness. We found significant associations between the location of these heat emergencies and urban heat islands as estimated from remotely-sensed surface and community science-derived air temperature metrics, but not a co-estimated heat index. We also found that available refuge facilities are insufficiently located to protect individuals with reduced mobility across areas with the highest number of heat-related health emergencies. Community involvement in the mitigation and management of extreme heat threats, especially for those disproportionately impacted, is necessary to decrease the number of summertime heat illnesses.

Cell-free biosynthesis combined with deep learning accelerates de novo-development of antimicrobial peptides.

Bioactive peptides are key molecules in health and medicine. Deep learning holds a big promise for the discovery and design of bioactive peptides. Yet, suitable experimental approaches are required to validate candidates in high throughput and at low cost. Here, we established a cell-free protein synthesis (CFPS) pipeline for the rapid and inexpensive production of antimicrobial peptides (AMPs) directly from DNA templates. To validate our platform, we used deep learning to design thousands of AMPs de novo. Using computational methods, we prioritized 500 candidates that we produced and screened with our CFPS pipeline. We identified 30 functional AMPs, which we characterized further through molecular dynamics simulations, antimicrobial activity and toxicity. Notably, six de novo-AMPs feature broad-spectrum activity against multidrug-resistant pathogens and do not develop bacterial resistance. Our work demonstrates the potential of CFPS for high throughput and low-cost production and testing of bioactive peptides within less than 24 h.

Recombinant Reporter Phage rTUN1::nLuc Enables Rapid Detection and Real-Time Antibiotic Susceptibility Testing of Klebsiella pneumoniae K64 Strains.

The emergence of multi-drug-resistant Klebsiella pneumoniae (Kp) strains constitutes an enormous threat to global health as multi-drug resistance-associated treatment failure causes high mortality rates in nosocomial infections. Rapid pathogen detection and antibiotic resistance screening are therefore crucial for successful therapy and thus patient survival. Reporter phage-based diagnostics offer a way to speed up pathogen identification and resistance testing as integration of reporter genes into highly specific phages allows real-time detection of phage replication and thus living host cells. Kp-specific phages use the host's capsule, a major virulence factor of Kp, as a receptor for adsorption. To date, 80 different Kp capsule types (K-serotypes) have been described with predominant capsule types varying between different countries and continents. Therefore, reporter phages need to be customized according to the locally prevailing variants. Recently, we described the autographivirus vB_KpP_TUN1 (TUN1), which specifically infects Kp K64 strains, the most predominant capsule type at the military hospital in Tunis (MHT) that is also associated with high mortality rates. In this work, we developed the highly specific recombinant reporter phage rTUN1::nLuc, which produces nanoluciferase (nLuc) upon host infection and thus enables rapid detection of Kp K64 cells in clinical matrices such as blood and urine. At the same time, rTUN1::nLuc allows for rapid antibiotic susceptibility testing and therefore identification of suitable antibiotic treatment in less than 3 h.

Evidence that oral immunoglobulins (KMP01) suppress pro-tumor inflammation in rectal carcinoma: Case report and treatment concept.

BACKGROUND: A female patient aged 49 years with a rectal adenocarcinoma underwent tumor resection and multiple follow-up surgical operations whilst receiving compassionate therapy with polyvalent immunoglobulins derived from bovine colostrum (KMP01), a potential modulator of the pro-tumor inflammatory response. AIMS: Assessment of safety of the treatment, effect on tumor recurrence, and effect on parameters associated with the pro-tumor inflammatory response. MATERIALS AND METHODS: The dose of KMP01 varied from 72 g daily in the perioperative period to 12 - 24 g daily thereafter. The pro-tumor inflammatory response was measured using changes in C-reactive protein (CRP) and the lymphocyte-monocyte ratio (LMR). RESULTS: Surgical intervention caused large increases in CRP (up to 400 mg/L) and decreases in the LMR (below target levels of 2.83). However, such changes rapidly returned to normal, where they remained during prolonged treatment with immunoglobulins. Despite the generally poor prognosis associated with a stenotic tumor, cachexia, and multiple surgery, there was no tumor recurrence during the 3-year follow-up. The condition of the patient is good, albeit with a reduced quality of life due to the stoma. CONCLUSION: Polyvalent immunoglobulins constitute a potential and safe prophylactic agent against the pro-tumor inflammatory response. This is the first time that polyvalent immunoglobulins have been used in a colorectal carcinoma patient. The findings can be a basis for further investigations.

Anatomically curated segmentation of human subcortical structures in high resolution magnetic resonance imaging: An open science approach.

Magnetic resonance imaging (MRI)-based brain segmentation has recently been revolutionized by deep learning methods. These methods use large numbers of annotated segmentations to train algorithms that have the potential to perform brain segmentations reliably and quickly. However, training data for these algorithms are frequently obtained from automated brain segmentation systems, which may contain inaccurate neuroanatomy. Thus, the neuroimaging community would benefit from an open source database of high quality, neuroanatomically curated and manually edited MRI brain images, as well as the publicly available tools and detailed procedures for generating these curated data. Manual segmentation approaches are regarded as the gold standard for brain segmentation and parcellation. These approaches underpin the construction of neuroanatomically accurate human brain atlases. In addition, neuroanatomically precise definitions of MRI-based regions of interest (ROIs) derived from manual brain segmentation are essential for accuracy in structural connectivity studies and in surgical planning for procedures such as deep brain stimulation. However, manual segmentation procedures are time and labor intensive, and not practical in studies utilizing very large datasets, large cohorts, or multimodal imaging. Automated segmentation methods were developed to overcome these issues, and provide high data throughput, increased reliability, and multimodal imaging capability. These methods utilize manually labeled brain atlases to automatically parcellate the brain into different ROIs, but do not have the anatomical accuracy of skilled manual segmentation approaches. In the present study, we developed a custom software module for manual editing of brain structures in the freely available 3D Slicer software platform that employs principles and tools based on pioneering work from the Center for Morphometric Analysis (CMA) at Massachusetts General Hospital. We used these novel 3D Slicer segmentation tools and techniques in conjunction with well-established neuroanatomical definitions of subcortical brain structures to manually segment 50 high resolution T1w MRI brains from the Human Connectome Project (HCP) Young Adult database. The structural definitions used herein are associated with specific neuroanatomical ontologies to systematically interrelate histological and MRI-based morphometric definitions. The resulting brain datasets are publicly available and will provide the basis for a larger database of anatomically curated brains as an open science resource.

Cell-free production of personalized therapeutic phages targeting multidrug-resistant bacteria.

Bacteriophages are potent therapeutics against biohazardous bacteria, which rapidly develop multidrug resistance. However, routine administration of phage therapy is hampered by a lack of rapid production, safe bioengineering, and detailed characterization of phages. Thus, we demonstrate a comprehensive cell-free platform for personalized production, transient engineering, and proteomic characterization of a broad spectrum of phages. Using mass spectrometry, we validated hypothetical and non-structural proteins and could also monitor the protein expression during phage assembly. Notably, a few microliters of a one-pot reaction produced effective doses of phages against enteroaggregative Escherichia coli (EAEC), Yersinia pestis, and Klebsiella pneumoniae. By co-expressing suitable host factors, we could extend the range of cell-free production to phages targeting gram-positive bacteria. We further introduce a non-genomic phage engineering method, which adds functionalities for only one replication cycle. In summary, we expect this cell-free methodology to foster reverse and forward phage engineering and customized production of clinical-grade bacteriophages.

Effect of lockdown and vaccination on the course of the COVID-19 pandemic in Germany.

BACKGROUND: Incidence(t), derived from observational data published by the Robert Koch Institute, Berlin, Germany, is a commonly used parameter to illustrate the course of the COVID-19 pandemic in Germany. The parameter tα(t), equivalent to the doubling-time of the virus described by our research group, has also been useful in this regard. AIMS: To identify and compare parameters suitable for monitoring the course of the pandemic and to evaluate the extent to which these reflect qualitatively and quantitatively the effects of interventional measures introduced to control the pandemic. MATERIALS AND METHODS: Parameters potentially useful for monitoring the course of the pandemic were obtained empirically or derived using the Bateman SIZ model and observational data for the daily increase in the number of new infections. The doubling-time in the number of infections, tα(t) was obtained by curve-fitting observational data for the previous 14-day interval and a fixed value for tbeta (half-life for rate of recovery = 6.24 days). The effects of the interventional measures on the course of the pandemic as reflected in the modulation of the identified parameters were evaluated. RESULTS: A total of 5 different parameters (Incidence(t), R9(t), tα_stable(S), Incidencecalc(t+14), tα(t)) of potential value in monitoring the course of the pandemic were identified. Lockdown measures altered Incidence(t), and these effects could be quantitated from alterations in the reproduction factor, R9(t), a parameter with prognostic value reflecting the consequences of non-intervention. The parameter tα_stable(S) is a function of the proportion of susceptible persons and therefore reflects the effects of vaccination. Although vaccination was in progress, together with lockdown and restrictions associated with the Recovered-Vaccinated-tested rule, R9(t) remained above 1.0 apparently due to the emergence of the more virulent Mδ variant (4th wave of the pandemic in Germany). CONCLUSION: i) The newly identified parameters provide qualitative and quantitative information on the course of the COVID-19 pandemic in Germany. ii) R9(t) is a suitable parameter for assessing the effects of interventional measures and may have prognostic value. iii) The parameter tα_stable(S), a function of the proportion of susceptible persons, reflects the effects of vaccination. iv) Incidencecalc(t+14) provides prognostic information on the projected course of the pandemic with the assumption that the factors driving the pandemic do not change and is recommended as a suitable parameter for making decisions in real-time, with minimum delay, whether lockdown measures should be implemented.

Reoccurring Bovine Anthrax in Germany on the Same Pasture after 12 Years.

The zoonotic disease anthrax, caused by the endospore-forming bacterium Bacillus anthracis, is very rare in Germany. In the state of Bavaria, the last case occurred in July of 2009, resulting in four dead cows. In August of 2021, the disease reemerged after heavy rains, killing one gestating cow. Notably, both outbreaks affected the same pasture, suggesting a close epidemiological connection. B. anthracis could be grown from blood culture, and the presence of both virulence plasmids (pXO1 and pXO2) was confirmed by PCR. Also, recently developed diagnostic tools enabled rapid detection of B. anthracis cells and nucleic acids directly in clinical samples. The complete genome of the strain isolated from blood, designated BF-5, was DNA sequenced and phylogenetically grouped within the B.Br.CNEVA clade, which is typical for European B. anthracis strains. The genome was almost identical to BF-1, the isolate from 2009, separated only by three single nucleotide polymorphisms (SNPs) on the chromosome, one on plasmid pXO2 and three indel regions. Further, B. anthracis DNA was detected by PCR from soil samples taken from spots in the pasture where the cow had fallen. New tools based on phage receptor-binding proteins enabled the microscopic detection and isolation of B. anthracis directly from soil samples. These environmental isolates were genotyped and found to be identical to BF-5 in terms of SNPs. Therefore, it seems that the BF-5 genotype is currently the prevalent one at the affected premises. The area contaminated by the cadaver was subsequently disinfected with formaldehyde.

In-Depth Analysis of Bacillus anthracis 16S rRNA Genes and Transcripts Reveals Intra- and Intergenomic Diversity and Facilitates Anthrax Detection.

Analysis of 16S rRNA (rRNA) genes provides a central means of taxonomic classification of bacterial species. Based on presumed sequence identity among species of the Bacillus cereus sensu lato group, the 16S rRNA genes of B. anthracis have been considered unsuitable for diagnosis of the anthrax pathogen. With the recent identification of a single nucleotide polymorphism in some 16S rRNA gene copies, specific identification of B. anthracis becomes feasible. Here, we designed and evaluated a set of in situ, in vitro, and in silico assays to assess the unknown 16S state of B. anthracis from different perspectives. Using a combination of digital PCR, fluorescence in situ hybridization, long-read genome sequencing, and bioinformatics, we were able to detect and quantify a unique 16S rRNA gene allele of B. anthracis (16S-BA-allele). This allele was found in all available B. anthracis genomes and may facilitate differentiation of the pathogen from any close relative. Bioinformatics analysis of 959 B. anthracis SRA data sets inferred that abundances and genomic arrangements of the 16S-BA-allele and the entire rRNA operon copy numbers differ considerably between strains. Expression ratios of 16S-BA-alleles were proportional to the respective genomic allele copy numbers. The findings and experimental tools presented here provide detailed insights into the intra- and intergenomic diversity of 16S rRNA genes and may pave the way for improved identification of B. anthracis and other pathogens with diverse rRNA operons. IMPORTANCE For severe infectious diseases, precise pathogen detection is crucial for antibiotic therapy and patient survival. Identification of Bacillus anthracis, the causative agent of the zoonosis anthrax, can be challenging when querying specific nucleotide sequences such as in small subunit rRNA (16S rRNA) genes, which are commonly used for typing of bacteria. This study analyzed on a broad genomic scale a cryptic and hitherto underappreciated allelic variant of the bacterium's 16S rRNA genes and their transcripts using a set of in situ, in vitro, and in silico assays and found significant intra- and intergenomic heterogeneity in the distribution of the allele and overall rRNA operon copy numbers. This allelic variation was uniquely species specific, which enabled sensitive pathogen detection on both DNA and transcript levels. The methodology used here is likely also applicable to other pathogens that are otherwise difficult to discriminate from their less harmful relatives.

COVID 19: Pandemic assessment and management using Incidencecalc(t+14) and herd immunity - Habere nos alia modum?

The course of the COVID-19 pandemic is commonly evaluated using the 7-day Incidence. We propose using 1) Incidencecalc(t+14), an index for the theoretical course of the pandemic in the absence of lockdown, as a basis for making real-time interventions. 2) The derived parameters tα(t) and tα_stable(S), obtained with the SIZ algorithm and the Bateman function, for estimating of the required degree of herd immunity to stop the pandemic. The current value of tα(t) for Germany is ~ 1.8 days, indicating that the percentage herd immunity required to halt the pandemic, assuming an efficacy of vaccination of 90%, is at least 87%.

Patient-specific connectomic models correlate with, but do not reliably predict, outcomes in deep brain stimulation for obsessive-compulsive disorder.

Deep brain stimulation (DBS) of the ventral internal capsule/ventral striatum (VCVS) is an emerging treatment for obsessive-compulsive disorder (OCD). Recently, multiple studies using normative connectomes have correlated DBS outcomes to stimulation of specific white matter tracts. Those studies did not test whether these correlations are clinically predictive, and did not apply cross-validation approaches that are necessary for biomarker development. Further, they did not account for the possibility of systematic differences between DBS patients and the non-diagnosed controls used in normative connectomes. To address these gaps, we performed patient-specific diffusion imaging in 8 patients who underwent VCVS DBS for OCD. We delineated tracts connecting thalamus and subthalamic nucleus (STN) to prefrontal cortex via VCVS. We then calculated which tracts were likely activated by individual patients' DBS settings. We fit multiple statistical models to predict both OCD and depression outcomes from tract activation. We further attempted to predict hypomania, a VCVS DBS complication. We assessed all models' performance on held-out test sets. With this best-practices approach, no model predicted OCD response, depression response, or hypomania above chance. Coefficient inspection partly supported prior reports, in that capture of tracts projecting to cingulate cortex was associated with both YBOCS and MADRS response. In contrast to prior reports, however, tracts connected to STN were not reliably correlated with response. Thus, patient-specific imaging and a guideline-adherent analysis were unable to identify a tractographic target with sufficient effect size to drive clinical decision-making or predict individual outcomes. These findings suggest caution in interpreting the results of normative connectome studies.

Ultrasensitive Detection of Bacillus anthracis by Real-Time PCR Targeting a Polymorphism in Multi-Copy 16S rRNA Genes and Their Transcripts.

The anthrax pathogen Bacillus anthracis poses a significant threat to human health. Identification of B. anthracis is challenging because of the bacterium's close genetic relationship to other Bacillus cereus group species. Thus, molecular detection is founded on species-specific PCR targeting single-copy genes. Here, we validated a previously recognized multi-copy target, a species-specific single nucleotide polymorphism (SNP) present in 2-5 copies in every B. anthracis genome analyzed. For this, a hydrolysis probe-based real-time PCR assay was developed and rigorously tested. The assay was specific as only B. anthracis DNA yielded positive results, was linear over 9 log10 units, and was sensitive with a limit of detection (LoD) of 2.9 copies/reaction. Though not exhibiting a lower LoD than established single-copy PCR targets (dhp61 or PL3), the higher copy number of the B. anthracis-specific 16S rRNA gene alleles afforded ≤2 unit lower threshold (Ct) values. To push the detection limit even further, the assay was adapted for reverse transcription PCR on 16S rRNA transcripts. This RT-PCR assay was also linear over 9 log10 units and was sensitive with an LoD of 6.3 copies/reaction. In a dilution series of experiments, the 16S RT-PCR assay achieved a thousand-fold higher sensitivity than the DNA-targeting assays. For molecular diagnostics, we recommend a real-time RT-PCR assay variant in which both DNA and RNA serve as templates (thus, no requirement for DNase treatment). This can at least provide results equaling the DNA-based implementation if no RNA is present but is superior even at the lowest residual rRNA concentrations.

Catching SARS-CoV-2 by Sequence Hybridization: a Comparative Analysis.

Controlling and monitoring the still ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic regarding geographical distribution, evolution, and emergence of new mutations of the SARS-CoV-2 virus is only possible due to continuous next-generation sequencing (NGS) and sharing sequence data worldwide. Efficient sequencing strategies enable the retrieval of increasing numbers of high-quality, full-length genomes and are, hence, indispensable. Two opposed enrichment methods, tiling multiplex PCR and sequence hybridization by bait capture, have been established for SARS-CoV-2 sequencing and are both frequently used, depending on the quality of the patient sample and the question at hand. Here, we focused on the evaluation of the sequence hybridization method by studying five commercially available sequence capture bait panels with regard to sensitivity and capture efficiency. We discovered the SARS-CoV-2-specific panel of Twist Bioscience to be the most efficient panel, followed by two respiratory panels from Twist Bioscience and Illumina, respectively. Our results provide on the one hand a decision basis for the sequencing community including a computation for using the full capacity of the flow cell and on the other hand potential improvements for the manufacturers. IMPORTANCE Sequencing the genomes of the circulating SARS-CoV-2 strains is the only way to monitor the viral spread and evolution of the virus. Two different approaches, namely, tiling multiplex PCR and sequence hybridization by bait capture, are commonly used to fulfill this task. This study describes for the first time a combined approach of droplet digital PCR (ddPCR) and NGS to evaluate five commercially available sequence capture panels targeting SARS-CoV-2. In doing so, we were able to determine the most sensitive and efficient capture panel, distinguish the mode of action of the various bait panels, and compute the number of read pairs needed to recover a high-quality full-length genome. By calculating the minimum number of read pairs needed, we are providing optimized flow cell loading conditions for all sequencing laboratories worldwide that are striving for maximizing sequencing output and simultaneously minimizing time, costs, and sequencing resources.

Enzyme-Linked Phage Receptor Binding Protein Assays (ELPRA) Enable Identification of Bacillus anthracis Colonies.

Bacteriophage receptor binding proteins (RBPs) are employed by viruses to recognize specific surface structures on bacterial host cells. Recombinant RBPs have been utilized for detection of several pathogens, typically as fusions with reporter enzymes or fluorescent proteins. Identification of Bacillus anthracis, the etiological agent of anthrax, can be difficult because of the bacterium's close relationship with other species of the Bacillus cereussensu lato group. Here, we facilitated the identification of B. anthracis using two implementations of enzyme-linked phage receptor binding protein assays (ELPRA). We developed a single-tube centrifugation assay simplifying the rapid analysis of suspect colonies. A second assay enables identification of suspect colonies from mixed overgrown solid (agar) media derived from the complex matrix soil. Thus, these tests identified vegetative cells of B. anthracis with little processing time and may support or confirm pathogen detection by molecular methods such as polymerase chain reaction.

COVID-19: Effect-modelling of vaccination in Germany with regard to the mutant strain B.1.1.7 and occupancy of ICU facilities.

BACKGROUND: The characteristics of the COVID-19 pandemic in Europe have changed since the initial outbreak in 2019 due to the emergence of more contagious mutant strains, notably the B.1.1.7 variant. This has resulted in the rapid implementation of vaccination programs in an effort to control the spread of the disease. AIMS: To model the effect of vaccination on the course of the pandemic in Germany taking into account observational data and the appearance of viral mutant B.1.1.7. MATERIALS AND METHODS: An effect model based on the Batman-SIZ algorithm was developed, taking into account both the parent and the B.1.1.7 mutant strains of the SARS-CoV-2 coronavirus and using input parameters obtained from observational data for January - March 2021. RESULTS: Effect-modelling using 3 different vaccination scenarios with different rates of vaccination involving 67 million persons (priority groups 1 - 5) and completed within 134 days compared to 318 days beginning February 24, 2021, showed a reduction in the number of infected persons from ca. 12.5 million to ca. 4.5 million with quantitively similar benefits regarding the occupancy and a critical burden on ICU facilities. CONCLUSION: The effect of vaccination in reducing the daily number of new infections, the total number of infections and the occupancy of intensive-care facilities in hospitals is proportional to the speed with which the target population are vaccinated.

COVID-19: Predictions for SARS-CoV-2 vaccination on the course of the pandemic and critical occupancy of intensive-care facilities in Germany.

AIMS OF THE STUDY: To obtain predictions using the Modified Bateman SIZ Model for the effects of vaccination on the course of the COVID-19 pandemic in Germany. MATERIALS AND METHODS: Start parameters for the model were obtained from observational data after data-smoothing to reduce between-day variation. Three scenarios, 1) no vaccination, 2) vaccination of 60% of the population over 12 months, 3) vaccination of 60% of the population over 7 months were examined. The effects of changes in tα (doubling-time for the spread of infection, known to be slower in the summer months) and tß (half-life of recovery from infection) on the daily number of infectious persons, the cumulative number of infected persons, and the duration of critical occupancy of intensive-care units were also determined. RESULTS: Vaccination produced a marked and rapid reduction in the number of infectious persons (up to -60%) and the total number of infected persons (up to -70%). A 7-month vaccination strategy was significantly more effective than a 12-month strategy. The summer effect came too late to have an additional effect on the spread of infection. Vaccination was predicted to reduce the duration of critical occupancy of intensive-care facilities by ~ 70%. DISCUSSION: The predictions are based on the assumptions that lockdown conditions are maintained and vaccine availability is not limiting. CONCLUSION: Predictions made using the model show that vaccination with a SARS-CoV-2 vaccine can markedly reduce the spread of the COVID-19 disease and the period of critical occupancy of intensive-care facilities in Germany.

Modelling Soluble Solids Content Accumulation in 'Braeburn' Apples.

Optical sensor data can be used to determine changes in anthocyanins, chlorophyll and soluble solids content (SSC) in apple production. In this study, visible and near-infrared spectra (729 to 975 nm) were transformed to SSC values by advanced multivariate calibration models i.e., partial least square regression (PLSR) in order to test the substitution of destructive chemical analyses through non-destructive optical measurements. Spectral field scans were carried out from 2016 to 2018 on marked 'Braeburn' apples in Southwest Germany. The study combines an in-depth statistical analyses of longitudinal SSC values with horticultural knowledge to set guidelines for further applied use of SSC predictions in the orchard to gain insights into apple carbohydrate physiology. The PLSR models were investigated with respect to sample size, seasonal variation, laboratory errors and the explanatory power of PLSR models when applied to independent samples. As a result of Monte Carlo simulations, PLSR modelled SSC only depended to a minor extent on the absolute number and accuracy of the wet chemistry laboratory calibration measurements. The comparison between non-destructive SSC determinations in the orchard with standard destructive lab testing at harvest on an independent sample showed mean differences of 0.5% SSC over all study years. SSC modelling with longitudinal linear mixed-effect models linked high crop loads to lower SSC values at harvest and higher SSC values for fruit from the top part of a tree.

Forensic mental health in Europe: some key figures.

PURPOSE: While the number of forensic beds and the duration of psychiatric forensic psychiatric treatment have increased in several European Union (EU) states, this is not observed in others. Patient demographics, average lengths of stay and legal frameworks also differ substantially. The lack of basic epidemiological information on forensic patients and of shared indicators on forensic care within Europe is an obstacle to comparative research. The reasons for such variation are not well understood. METHODS: Experts from seventeen EU states submitted data on forensic bed prevalence rates, gender distributions and average length of stay in forensic in-patient facilities. Average length of stay and bed prevalence rates were examined for associations with country-level variables including Gross Domestic Product (GDP), expenditure on healthcare, prison population, general psychiatric bed prevalence rates and democracy index scores. RESULTS: The data demonstrated substantial differences between states. Average length of stay was approximately ten times greater in the Netherlands than Slovenia. In England and Wales, 18% of patients were female compared to 5% in Slovenia. There was a 17-fold difference in forensic bed rates per 100,000 between the Netherlands and Spain. Exploratory analyses suggested average length of stay was associated with GDP, expenditure on healthcare and democracy index scores. CONCLUSION: The data presented in this study represent the most recent overview of key epidemiological data in forensic services across seventeen EU states. However, systematically collected epidemiological data of good quality remain elusive in forensic psychiatry. States need to develop common definitions and recording practices and contribute to a publicly available database of such epidemiological indicators.