Shaping the laser control landscape of a hydrogen transfer reaction by vibrational strong coupling. A direct optimal control approach.

Controlling molecular reactivity by shaped laser pulses is a long-standing goal in chemistry. Here, we suggest a direct optimal control approach that combines external pulse optimization with other control parameters arising in the upcoming field of vibro-polaritonic chemistry for enhanced controllability. The direct optimal control approach is characterized by a simultaneous simulation and optimization paradigm, meaning that the equations of motion are discretized and converted into a set of holonomic constraints for a nonlinear optimization problem given by the control functional. Compared with indirect optimal control, this procedure offers great flexibility, such as final time or Hamiltonian parameter optimization. A simultaneous direct optimal control theory will be applied to a model system describing H-atom transfer in a lossy Fabry-Pérot cavity under vibrational strong coupling conditions. Specifically, optimization of the cavity coupling strength and, thus, of the control landscape will be demonstrated.

Nectar traits differ between pollination syndromes in Balsaminaceae.

BACKGROUND AND AIMS: The attractiveness of nectar rewards depends both on the quantity of nectar produced and on its chemical composition. It is known that nectar quantity and chemical composition can differ in plant species depending on the main pollinator associated with the species. The main aims of this study were to test formally whether nectar traits are adapted to pollination syndromes in the speciose Balsaminaceae and, if so, whether a combination of nectar traits mirrors pollination syndromes. METHODS: Comparative methods based on Ornstein-Uhlenbeck models were used to test whether nectar volume, nectar sucrose proportion, sugar and amino acid concentration and amino acid composition had evolved as a function of pollination syndromes in 57 species of Balsaminaceae. Cluster analysis and ordination were performed to derive clusters of species resembling each other in nectar composition. KEY RESULTS: Evolutionary models for nectar volume and nectar sucrose proportion performed best when including information on pollination syndrome, while including such information improve model fit neither for sugar and amino acid concentration nor for amino acid composition. A significant relationship emerged between pollination syndrome and the combined nectar traits. CONCLUSIONS: Our results show that nectar volume and nectar sucrose proportion evolve rapidly towards optimal values associated with different pollination syndromes. The detection of a signal indicating that nectar traits in combination are to a certain extent able to predict pollination syndromes in Balsaminaceae suggests that a holistic approach including the whole set of nectar traits helps us to better understand evolution of nectar composition in response to pollinators.

A quantum-mechanical tier model for phonon-driven vibrational relaxation dynamics of adsorbates at surfaces.

We present a quantum-mechanical tier model for vibrational relaxation of low-lying excited states of an adsorbate vibrational mode (system), coupled to surface phonons (bath), at zero temperature. The tier model, widely used in studies of intramolecular vibrational energy redistribution in polyatomics, is adapted here to adsorbate-surface systems with the help of an embedded cluster approach, using orthogonal coordinates for the system and bath modes, and a phononic expansion of their interaction. The key idea of the model is to organize the system-bath zeroth-order vibrational space into a hierarchical structure of vibrational tiers and keep therein only vibrational states that are sequentially generated from the system-bath initial vibrational state. Each tier is generated from the previous one by means of a successor operator, derived from the system-bath interaction Hamiltonian. This sequential procedure leads to a drastic reduction of the dimension of the system-bath vibrational space. We notably show that for harmonic vibrational motion of the system and linear system-bath couplings in the system coordinate, the dimension of the tier-model vibrational basis scales as ∼Nl×υ. Here, N is the number of bath modes, l is the highest-order of the phononic expansion, and υ is the size of the system vibrational basis. This polynomial scaling is computationally far superior to the exponential scaling of the original zeroth-order vibrational basis, ∼MN, with M being the number of basis functions per bath mode. In addition, since each tier is coupled only to its adjacent neighbors, the matrix representation of the system-bath Hamiltonian in this new vibrational basis has a symmetric block-tridiagonal form, with each block being very sparse. This favors the combination of the tier-model with iterative Krylov techniques, such as the Lanczos algorithm, to solve the time-dependent Schrödinger equation for the full Hamiltonian. To illustrate the method, we study vibrational relaxation of a D-Si bending mode, coupled via two- and (mainly) one-phonon interactions to a fully D-covered Si(100)-(2 × 1) surface, using a recent first-principles system-bath Hamiltonian. The results of the tier model are compared with those obtained by the Lindblad formalism of the reduced density matrix. We find that the tier model provides much more information and insight into mechanisms of vibration-phonon couplings at surfaces, and gives more reliable estimates of the adsorbate vibrational lifetimes. Moreover, the tier model might also serve as a benchmark for other approximate quantum-dynamics methods, such as multiconfiguration wavefunction approaches.

Acute health effects of desktop 3D printing (fused deposition modeling) using acrylonitrile butadiene styrene and polylactic acid materials: An experimental exposure study in human volunteers.

3D printers are increasingly run at home. Nanoparticle emissions from those printers have been reported, which raises the question whether adverse health effects from ultrafine particles (UFP) can be elicited by 3D printers. We exposed 26 healthy adults in a single-blinded, randomized, cross-over design to emissions of a desktop 3D printer using fused deposition modeling (FDM) for 1 hour (high UFP-emitting acrylonitrile butadiene styrene [ABS] vs low-emitting polylactic acid [PLA]). Before and after exposures, cytokines (IL-1ß, IL-6, TNF-α, INF-γ) and ECP in nasal secretions, exhaled nitric oxide (FeNO), urinary 8-isoprostaglandin F2α (8-iso PGF2α ), and self-reported symptoms were assessed. The exposures had no significant differential effect on 8-iso PGF2α and nasal biomarkers. However, there was a difference (P < .05) in the time course of FeNO, with higher levels after ABS exposure. Moreover, indisposition and odor nuisance were increased for ABS exposure. These data suggest that 1 hour of exposure to 3D printer emissions had no acute effect on inflammatory markers in nasal secretions and urine. The slight relative increase in FeNO after ABS printing compared to PLA might be due to eosinophilic inflammation from inhaled UFP particles. This possibility should be investigated in further studies using additional biomarkers and longer observation periods.

Plasticity and evolution in correlated suites of traits.

When organisms are faced with new or changing environments, a central challenge is the coordination of adaptive shifts in many different phenotypic traits. Relationships among traits may facilitate or constrain evolutionary responses to selection, depending on whether the direction of selection is aligned or opposed to the pattern of trait correlations. Attempts to predict evolutionary potential in correlated traits generally assume that correlations are stable across time and space; however, increasing evidence suggests that this may not be the case, and flexibility in trait correlations could bias evolutionary trajectories. We examined genetic and environmental influences on variation and covariation in a suite of behavioural traits to understand if and how flexibility in trait correlations influences adaptation to novel environments. We tested the role of genetic and environmental influences on behavioural trait correlations by comparing Trinidadian guppies (Poecilia reticulata) historically adapted to high- and low-predation environments that were reared under native and non-native environmental conditions. Both high- and low-predation fish exhibited increased behavioural variance when reared under non-native vs. native environmental conditions, and rearing in the non-native environment shifted the major axis of variation among behaviours. Our findings emphasize that trait correlations observed in one population or environment may not predict correlations in another and that environmentally induced plasticity in correlations may bias evolutionary divergence in novel environments.

Pollen-based quantitative reconstructions of Holocene regional vegetation cover (plant-functional types and land-cover types) in Europe suitable for climate modelling.

We present quantitative reconstructions of regional vegetation cover in north-western Europe, western Europe north of the Alps, and eastern Europe for five time windows in the Holocene [around 6k, 3k, 0.5k, 0.2k, and 0.05k calendar years before present (bp)] at a 1° × 1° spatial scale with the objective of producing vegetation descriptions suitable for climate modelling. The REVEALS model was applied on 636 pollen records from lakes and bogs to reconstruct the past cover of 25 plant taxa grouped into 10 plant-functional types and three land-cover types [evergreen trees, summer-green (deciduous) trees, and open land]. The model corrects for some of the biases in pollen percentages by using pollen productivity estimates and fall speeds of pollen, and by applying simple but robust models of pollen dispersal and deposition. The emerging patterns of tree migration and deforestation between 6k bp and modern time in the REVEALS estimates agree with our general understanding of the vegetation history of Europe based on pollen percentages. However, the degree of anthropogenic deforestation (i.e. cover of cultivated and grazing land) at 3k, 0.5k, and 0.2k bp is significantly higher than deduced from pollen percentages. This is also the case at 6k in some parts of Europe, in particular Britain and Ireland. Furthermore, the relationship between summer-green and evergreen trees, and between individual tree taxa, differs significantly when expressed as pollen percentages or as REVEALS estimates of tree cover. For instance, when Pinus is dominant over Picea as pollen percentages, Picea is dominant over Pinus as REVEALS estimates. These differences play a major role in the reconstruction of European landscapes and for the study of land cover-climate interactions, biodiversity and human resources.

Site-Specific Conjugation of Monomethyl Auristatin E to Anti-CD30 Antibodies Improves Their Pharmacokinetics and Therapeutic Index in Rodent Models.

Antibody-drug conjugates (ADCs) have demonstrated clinical benefits that have led to the recent FDA approval of KADCYLA and ADCETRIS. Most ADCs that are currently in clinical use or development, including ADCETRIS, are produced by chemical conjugation of a toxin via either lysine or cysteine residues, inevitably leading to heterogeneous products with variable drug-to-antibody ratios (DARs). Here, we describe the in vitro and in vivo characterization of four novel ADCs that are based on the anti-CD30 antibody cAC10, which has the same polypeptide backbone as ADCETRIS, and compare the results with the latter. Bacterial transglutaminase (BTG) was exploited to site-specifically conjugate derivatives of monomethyl auristatin E (all comprising a cleavable linker) to the glutamine at positions 295 and 297 of cAC10, thereby yielding homogeneous ADCs with a DAR of 4. In vitro cell toxicity experiments using two different CD30-positive cell lines (Karpas 299 and Raji-CD30(+)) revealed comparable EC50 values for ADCETRIS (1.8 ± 0.4 and 3.6 ± 0.6 ng/mL, respectively) and the four cAC10-based ADCs (2.0 ± 0.4 to 4.9 ± 1.0 ng/mL). Quantitative time-dependent in vivo biodistribution studies (3-96 h p.i.) in normal and xenografted (Karpas 299 cells) SCID mice were performed with a selected (125)I-radioiodinated cAC10 ADC and compared with that of (125)I-ADCETRIS. The chemo-enzymatically conjugated, radioiodinated ADC showed higher tumor uptake (17.84 ± 2.2% ID/g 24 h p.i.) than (125)I-ADCETRIS (10.5 ± 1.8% ID/g 24 h p.i.). Moreover, (125)I-ADCETRIS exhibited higher nontargeted liver and spleen uptake. In line with these results, the maximum tolerated dose of the BTG-coupled ADC (>60 mg/kg) was significantly higher than that of ADCETRIS (18 mg/kg) in rats. These results suggest that homogeneous ADCs display improved pharmacokinetics and better therapeutic indexes compared to those of chemically modified ADCs with variable DARs.

A spatiotemporal model to assess the introduction risk of African horse sickness by import of animals and vectors in France.

BACKGROUND: African horse sickness (AHS) is a major, Culicoides-borne viral disease in equines whose introduction into Europe could have dramatic consequences. The disease is considered to be endemic in sub-Saharan Africa. Recent introductions of other Culicoides-borne viruses (bluetongue and Schmallenberg) into northern Europe have highlighted the risk that AHS may arrive in Europe as well. The aim of our study was to provide a spatiotemporal quantitative risk model of AHS introduction into France. The study focused on two pathways of introduction: the arrival of an infectious host (PW-host) and the arrival of an infectious Culicoides midge via the livestock trade (PW-vector). The risk of introduction was calculated by determining the probability of an infectious animal or vector entering the country and the probability of the virus then becoming established: i.e., the virus's arrival in France resulting in at least one local equine host being infected by one local vector. This risk was assessed using data from three consecutive years (2010 to 2012) for 22 regions in France. RESULTS: The results of the model indicate that the annual risk of AHS being introduced to France is very low but that major spatiotemporal differences exist. For both introduction pathways, risk is higher from July to October and peaks in July. In general, regions with warmer climates are more at risk, as are colder regions with larger equine populations; however, regional variation in animal importation patterns (number and species) also play a major role in determining risk. Despite the low probability that AHSV is present in the EU, intra-EU trade of equines contributes most to the risk of AHSV introduction to France because it involves a large number of horse movements. CONCLUSION: It is important to address spatiotemporal differences when assessing the risk of ASH introduction and thus also when implementing efficient surveillance efforts. The methods and results of this study may help develop surveillance techniques and other risk reduction measures that will prevent the introduction of AHS or minimize AHS' potential impact once introduced, both in France and the rest of Europe.

Assay characteristics influence the aldosterone to renin ratio as a screening tool for primary aldosteronism: results of the German Conn's registry.

Primary aldosteronism (PA) is the most frequent cause of secondary arterial hypertension. The aldosterone to renin ratio (ARR) is the gold standard for screening, but variability between biochemical methods used remains of concern. The aim of the study was to analyze center-specific features of biochemical diagnostic strategies prior to the 2008 consensus within the German Conn's Registry. The study was designed as a retrospective study in 5 tertiary care hospitals. Patients analyzed for PA between 1990 and 2006 were studied. Characteristics of the assays used to determine ARR during establishing the diagnosis of PA were analyzed in the retrospective part of the German Conn's Registry. Eighty-six out of 484 documented ARR values had to be excluded from further evaluations because the laboratory or the assays were unknown. In the remaining 398 patients ARR was determined using 10 different assay combinations in the centers (aldosterone plus plasma renin activity or concentration). Considerable differences were seen between the mean concentrations for aldosterone (p<0.0001), renin concentration (p<0.001), and renin activity (p=0.009) for the different assays. The differences between the absolute concentrations measured by the different assays also had significant impact upon the resulting mean ratios. If published cutoff values are applied, the use of different commercial assays to determine the ARR in clinical routine results in major differences in positive screening rates. This heterogeneity affects sensitivity and specificity of screening for PA. Our data emphasize the importance of standardized screening procedures, which must include standardization of biochemical methods.

Occupation as means and ends in paediatric occupational therapy - A systematic review.

BACKGROUND: There is a lack of evidence-based knowledge in paediatric occupational therapy about the effectiveness of interventions using daily activities as a treatment modality in improving children's participation. OBJECTIVE: This study aimed to evaluate the effectiveness of occupation-based and occupation-focused interventions in improving participation in everyday occupations for young children with a disability. MATERIAL AND METHODS: A systematic review based on Joanna Briggs Institute methodology and critical appraisal tools was conducted. Six databases were searched for quantitative intervention studies aimed at improving participation in everyday occupations of young children with a disability through the use of everyday occupation. RESULTS: The search yielded 3732 records, of which 13 studies met inclusion criteria. Ten studies met methodological quality criteria and were included in the synthesis, five randomised controlled trials and five quasi-experimental studies, involving a total of 424 children with a mean age of 6.5 years. The studies were classified into cognitive (n = 5), context-focussed (n = 2) and playgroup interventions (n = 3). Study quality ranged from low to moderate, only one study was rated high quality. CONCLUSIONS AND SIGNIFICANCE: Occupation-based and occupation-focused interventions may have a positive effect on participation in everyday occupations for young children with a disability, but study design, risk of bias and insufficient reporting limit confidence in the body of evidence.

[The clinical importance of the critical view of safety in laparoscopic cholecystectomy]. / Die klinische Bedeutung des "critical view of safety" in der laparoskopischen Gallenblasenchirurgie.

BACKGROUND: Injury of the bile duct during cholecystectomy (CHE) is a severe complication. The critical view of safety (CVS) can help to reduce the frequency of this complication during laparoscopic CHE. So far, no scoring of CVS images with a grading system is available. METHOD: The CVS images of 534 patients with laparoscopic CHE could be structurally analyzed and assessed with marks from 1 (very good) to 5 (insufficient). The CVS mark was correlated with the perioperative course. Additionally, the perioperative course of patients after laparoscopic CHE with and without a CVS image was investigated. RESULTS: In 534 patients 1 or more CVS images could be analyzed. The average CVS mark was 1.9, whereby 280 patients (52.4%) had a 1, 126 patients (23.6%) a 2, 114 (21.3%) a 3 and 14 patients (2.6%) a 4 or 5. Younger patients with elective laparoscopic CHE had CVS images significantly more frequently (p ≤ 0.04). The statistical examination with Pearson's χ2-test and the F­test (ANOVA) showed a significant correlation between improving CVS marks and reduction of surgery time (p < 0.01) and the hospitalization time (p < 0.01). For senior physicians the quota of CVS images ranged from 71% to 92% and the average marks from 1.5 to 2.2. The marks for the CVS images were significantly better for female than male patients (1.8 vs. 2.1, p < 0.01). DISCUSSION: There was a relatively broad distribution of marks for CVS images. Injuries of the bile duct can be avoided with a high degree of certainty with marks 1­2 for the CVS image. The CVS is not always adequately visualized in laparoscopic CHE.

[The COVID-19 pandemic had significant impact on duration of surgery and hospitalization time for patients after cholecystectomy]. / Die Auswirkungen der COVID-19 Pandemie führten zu signifikanten Veränderungen der Operations- und Liegezeiten bei Patienten nach Cholezystektomie.

BACKGROUND: The COVID-19 pandemic made substantial changes in medical care necessary. The aims of this study were to find out what influence the pandemic had on the perioperative course in patients with cholecystectomy (CHE) and to highlight possible residual consequences. METHOD: From 1 July 2018 to 31 December 2021 a total of 735 patients with CHE were analyzed. Up to 21 March 2020 patients were assigned to the regular patient group (Reg, n = 430), patients after this date (first lockdown 22 March 2020) to the Cov19 patient group (Cov19, n = 305) and the 2 groups were compared. RESULTS: The average age of all patients was 59 years and 63% were women. The average length of hospitalization (KrVD, time period between surgery and discharge) was 4.4 days. The patient groups Reg and Cov19 did not differ with respect to age, gender or KrVD. The total number of CHEs carried out was reduced by 21.4% in the Cov19 group. This affected elective and emergency CHE to the same extent. The length of surgery significantly increased in the Cov19 group from 64 min (SD 34 min) to 71 min (SD 38 min). The number of short and long hospital stays (KrVD 2 or >4 days) significantly increased in the Cov19 group from 4 % to 20 % (short stay, p < 0.01) and from 23 % to 27 % (long stay, p < 0.01). This was particularly observed for patients >70 years old with an increase in long stays from 43 % to 56 % in the Cov19 group. CONCLUSION: The COVID-19 pandemic led to a clear reduction in CHE both for elective and emergency interventions. Furthermore, a significant lengthening of the surgery and hospitalization times could be observed for older patients. The residual consequences of the pandemic could be shortened hospitalization times after uncomplicated CHE and more interventional treatment procedures in complex cases.

Storylines for unprecedented heatwaves based on ensemble boosting.

Recent temperature extremes have shattered previously observed records, reaching intensities that were inconceivable before the events. Could the possibility of an event with such unprecedented intensity as the 2021 Pacific Northwest heatwave have been foreseen, based on climate model information available before the event? Could the scientific community have quantified its potential intensity based on the current generation of climate models? Here, we demonstrate how an ensemble boosting approach can be used to generate physically plausible storylines of a heatwave hotter than observed in the Pacific Northwest. We also show that heatwaves of much greater intensities than ever observed are possible in other locations like the Greater Chicago and Paris regions. In order to establish confidence in storylines of 'black swan'-type events, different lines of evidence need to be combined along with process understanding to make this information robust and actionable for stakeholders.

Multimodal imaging of pancreatic beta cells in vivo by targeting transmembrane protein 27 (TMEM27).

AIMS/HYPOTHESIS: Non-invasive diagnostic tools specific for pancreatic beta cells will have a profound impact on our understanding of the pathophysiology of metabolic diseases such as diabetes. The objective of this study was to use molecular imaging probes specifically targeting beta cells on human samples and animal models using state-of-the-art imaging modalities (fluorescence and PET) with preclinical and clinical perspective. METHODS: We generated a monoclonal antibody, 8/9-mAb, targeting transmembrane protein 27 (TMEM27; a surface N-glycoprotein that is highly expressed on beta cells), compared its expression in human and mouse pancreas, and demonstrated beta cell-specific binding in both. In vivo imaging was performed in mice with subcutaneous insulinomas overexpressing the human TMEM27 gene, or transgenic mice with beta cell-specific hTMEM27 expression under the control of rat insulin promoter (RIP-hTMEM27-tg), using fluorescence and radioactively labelled antibody, followed by tissue ex vivo analysis and fluorescence microscopy. RESULTS: Fluorescently labelled 8/9-mAb showed beta cell-specific staining on human and mouse pancreatic sections. Real-time PCR on islet cDNA indicated about tenfold higher expression of hTMEM27 in RIP-hTMEM27-tg mice than in humans. In vivo fluorescence and PET imaging in nude mice with insulinoma xenografts expressing hTMEM27 showed high 8/9-mAb uptake in tumours after 72 h. Antibody homing was also observed in beta cells of RIP-hTMEM27-tg mice by in vivo fluorescence imaging. Ex vivo analysis of intact pancreas and fluorescence microscopy in beta cells confirmed these findings. CONCLUSIONS/INTERPRETATION: hTMEM27 constitutes an attractive target for in vivo visualisation of pancreatic beta cells. Studies in mouse insulinoma models and mice expressing hTMEM27 demonstrate the feasibility of beta cell-targeted in vivo imaging, which is attractive for preclinical investigations and holds potential in clinical diagnostics.

Substance use and sexual risk behaviour among HIV-positive men who have sex with men in specialized out-patient clinics.

OBJECTIVES: Unprotected sexual intercourse between men who have sex with men (MSM) is the most common route of HIV infection in Germany. Approximately 70% of newly infected people are MSM. Substance use is a determinant of sexual risk behaviour in the general population, but also in the MSM subpopulation. There are only a few studies, from the USA, on the correlation between substance use and sexual risk behaviour in HIV-infected MSM in specialized care. METHODS: In a German sample of 445 HIV-infected MSM treated in specialized out-patient clinics, the influence of substance use on sexual risk behaviour was investigated. Information was obtained from subjects using self-report questionnaires and a structured interview. RESULTS: Recreational drug use was common. The prevalences of cannabis addiction (4.5%), harmful use of cannabis (4.3%) and harmful use of dissociative anaesthetics (0.4%) were higher than in the general German male population. A substantial proportion of patients reported unprotected insertive (32.9%) and receptive (34.6%) anal intercourse during the last 12 months. Use of cannabis, amyl nitrite, dissociative anaesthetics, cocaine, amphetamines and erectile dysfunction medication was significantly correlated with unprotected sexual contacts. Substance use in the context of sexual activity significantly increased sexual risk behaviour. CONCLUSIONS: Substance use, especially in the context of sexual activity, should be taken into account when developing new prevention and intervention programmes aimed at reducing sexual risk behaviour in HIV-infected MSM currently in specialized care.

The prevalence of familial hyperaldosteronism in apparently sporadic primary aldosteronism in Germany: a single center experience.

Primary aldosteronism (PA) is the most frequent cause of secondary arterial hypertension. To date 3 forms of familial hyperaldosteronism (FH) have been described accounting for a small percentage of all PA cases. In Germany, the prevalence of FH is currently unknown. Our aim was to determine the prevalence of familiarity in a large cohort of patients with PA. A total of 166 patients with apparently sporadic PA in Munich were investigated. FH types I, II, and III were identified using established clinical, biochemical, and molecular criteria. Among the 166 patients with PA, 2 patients (1.2%) reported a family history suggestive of FH. None of the 166 patients showed clinical, endocrine, or genetic evidence of FH type I. The 2 families had characteristic features of FH type II. Family A had 3 subjects affected out of 11 evaluated family members. Family B had 3 out of 4. Bilateral adrenal hyperplasia and unilateral adrenal adenoma were found within the same family. FH type I and FH type III are rare in Germany. With a prevalence of 1.2%, FH type II seems to be more common in apparently sporadic PA than had been assumed so far.

The role of the ocean in the global atmospheric budget of acetone.

Acetone is one of the most abundant carbonyl compounds in the atmosphere and it plays an important role in atmospheric chemistry. The role of the ocean in the global atmospheric acetone budget is highly uncertain, with past studies reaching opposite conclusions as to whether the ocean is a source or sink. Here we use a global 3-D chemical transport model (GEOS-Chem) simulation of atmospheric acetone to evaluate the role of air-sea exchange in the global budget. Inclusion of updated (slower) photolysis loss in the model means that a large net ocean source is not needed to explain observed acetone in marine air. We find that a simulation with a fixed seawater acetone concentration of 15 nM based on observations can reproduce the observed global patterns of atmospheric concentrations and air-sea fluxes. The Northern Hemisphere oceans are a net sink for acetone while the tropical oceans are a net source. On a global scale the ocean is in near-equilibrium with the atmosphere. Prescribing an ocean concentration of acetone as a boundary condition in the model assumes that ocean concentrations are controlled by internal production and loss, rather than by air-sea exchange. An implication is that the ocean plays a major role in controlling atmospheric acetone. This hypothesis needs to be tested by better quantification of oceanic acetone sources and sinks.

Derivation of a Floquet formalism within a natural framework.

Many biological systems experience a periodic environment. Floquet theory is a mathematical tool to deal with such time periodic systems. It is not often applied in biology, because linkage between the mathematics and the biology is not available. To create this linkage, we derive the Floquet theory for natural systems. We construct a framework, where the rotation of the Earth is causing the periodicity. Within this framework the angular momentum operator is introduced to describe the Earth's rotation. The Fourier operators and the Fourier states are defined to link the rotation to the biological system. Using these operators, the biological system can be transformed into a rotating frame in which the environment becomes static. In this rotating frame the Floquet solution can be derived. Two examples demonstrate how to apply this natural framework.

A pilot trial of quetiapine, lithium, or placebo added to divalproex sodium for hypomanic or manic episodes in ambulatory adults with bipolar I disorder.

BACKGROUND: Many patients with bipolar I disorder do not respond to monotherapy treatment with mood-stabilizing medications, and combination regimens are commonly used in both inpatient and outpatient settings for the acute and maintenance treatment of bipolar disorder. We studied whether combination therapy is more effective than monotherapy for the acute treatment of subjects with bipolar I disorder currently experiencing manic symptoms. The primary hypothesis was that combination treatments would be associated with greater reductions in symptoms of mania and hypomania than monotherapy alone. The secondary hypothesis was that combination therapies would be associated with lower depression levels than monotherapy alone. Last, a post-hoc exploratory aim was used to examine whether the effect of side effect severity on risk-of-dropout would be greater in combination therapies than in monotherapy alone. RESULTS: In this 12-week, double-blind, placebo-controlled ambulatory pilot trial, participants (n = 75) with bipolar I disorder were randomly assigned to: (1) monotherapy divalproex plus placebo (DVP + PBO), (2) combination therapy of divalproex plus blinded lithium (DVP + Li) or (3) divalproex plus blinded quetiapine (DVP + QTP). Combination therapies (vs. monotherapy) were not associated with improved symptoms of mania, hypomania or depression. The effect of side effect severity on study retention did not differ between combination therapies and monotherapy. However, the risk-of-dropout was significantly greater in the DVP + Li arm versus the DVP + PBO arm. CONCLUSIONS: No longitudinal differences in mania, hypomania or depression were found between combination therapies and monotherapy. The effect of side effect severity on study retention did not differ between groups. Due to the small sample size and differential rates of attrition between treatment arms, results of this pilot trial must be interpreted with caution. Trial registration ClinicalTrials.gov identifier: NCT00183443.

Gargle pool PCR testing in a hospital during medium and high SARS-CoV-2 incidence.

BACKGROUND: Hospitals need to be protected from SARS-CoV-2 infections to protect vulnerable patients. Thus, a safe, efficient, and cost-effective SARS-CoV-2 testing system for hospitals, in addition to standard hygiene measures and vaccination of staff, is necessary. Here we report on the feasibility and performance of a pool real-time reverse-transcriptase polymerase-chain-reaction (rRT-PCR) test system at, medium and high incidence. METHODS: We implemented a testing concept based on gargling at home and pooling of samples in the hospital before PCR testing in the laboratory. We used two PCR systems (point of care and standard 96-well plate system) to adapt to challenges in the hospital setting and respond to a rising incidence in the Omicron wave. FINDINGS: During our 10-week study period, we performed 697 pool PCRs (8793 tests in total) and identified 65 asymptomatic staff members by pool PCR and 94 symptomatic staff members by positive individual PCR. Virus loads in those detected by pool testing were significantly lower (P<0.001). The test system remained workable even during the peak of the Omicron wave and no outbreaks occurred in any specific area of the hospital during the study period. Unvaccinated individuals were over-represented in the positively tested (37% vs 22% positive tests, P=0.04). The test procedure was well accepted by a majority of the hospital staff (84%). CONCLUSION: Repeated gargle pool rRT-PCR testing can be implemented quickly in hospitals and is an effective, easily adaptable and well-accepted test system for hospitals, even during phases with very high infection rates.