A generic approach to estimate airborne concentrations of substances released by indoor spray processes using a deterministic 2-box model.

Sprays are used both in workplace and consumer settings. Although spraying has advantages, such as uniform distribution of substances on surfaces in a highly efficient manner, it is often associated with a high inhalation burden. For an adequate risk assessment, this exposure has to be reliably quantified. Exposure models of varying complexity are available, which are applicable to spray applications. However, a need for improvement has been identified. In this contribution, a simple 2-box approach is suggested for the assessment of the time-weighted averaged exposure concentration (TWA) using a minimum of input data. At the moment, the model is restricted to binary spray liquids composed of a non-volatile fraction and volatile solvents. The model output can be refined by introducing correction factors based on the classification and categorization of two key parameters, the droplet size class and the vapor pressure class of the solvent, or by using a data set of experimentally determined airborne release fractions related to the used spray equipment. A comparison of model results with measured data collected at real workplaces showed that this simple model based on readily available input parameters is very useful for screening purposes. The generic 2-box spray model without refinement overestimates the measurements of the considered scenarios in approximately 50% of the cases by more than a factor of 100. The generic 2-box model performs better for room spraying than for surface spraying, as the airborne fraction in the latter case is clearly overestimated. This conservatism of the prediction was significantly reduced when correction factors or experimentally determined airborne release fractions were used in addition to the generic input parameters. The resulting predictions still overestimate the exposure (ratio tool estimate to measured TWA > 10) or they are accurate (ratio 0.5-10). If the available information on boundary conditions (application type, equipment) does not justify the usage of airborne release fraction, room spraying should be used resulting in the highest exposure estimate. The model scope may be extended to (semi)volatile substances. However, acceptance may be compromised by the limited availability of measured data for this group of substances and thus may have limited potency to evaluate the model prediction.

Quantifying Exhaled Particles in Healthy Humans During Various Respiratory Activities Under Realistic Conditions.

Background: Quantitatively collecting and characterizing exhaled aerosols is vital for infection risk assessment, but the entire droplet size spectrum has often been neglected. We analyzed particle number and size distribution of healthy participants in various respiratory activities, considering inter-individual variability, and deployed a simplified far-field model to inform on infection risks. Methods: Participants repeated the same respiratory activities on two visits. Particles were collected using an airtight extraction helmet supplied with High Efficiency Particulate Air (HEPA) filtered air. The sampling volume flow was transported to two particle counters covering the small and large particle spectrum. The applied simple mass balance model included respiratory activity, viral load, room size, and air exchange rates. Results: Thirty participants completed the study. The major fraction of the number-based size distribution was <5 µm in all respiratory activities. In contrast, the major fraction of the volume-based size distribution was 2-12 µm in tidal breathing, but >60 µm in all other activities. Aerosol volume flow was lowest in tidal breathing, 10-fold higher in quiet/normal speaking, deep breathing, coughing, and 100-fold higher in loud speaking/singing. Intra-individual reproducibility was high. Between participants, aerosol volume flow varied by two orders of magnitude in droplets <80 µm, and three orders of magnitude in droplets >80 µm. Simple model calculations not accounting for potential particle size-dependent differences in viral load and infection-related differences were used to model airborne pathogen concentrations. Conclusions: Quantitative analysis of exhaled aerosols for the entire droplet size spectrum as well as the variability in aerosol emission between individuals provides information that can support infection research. Clinical Trial Registration number: NCT04771585.

Development of a non-target strategy for evaluation of potential biological effects of inhalable aerosols generated during purposeful room conditioning using an in vitro inhalation model.

OBJECTIVES: An integrated in vitro inhalation approach was outlined to estimate potential adverse acute inhalation effects of aerosols from commercial nebulizer applications used for purposeful room conditioning such as disinfection, scenting or others. Aerosol characterization, exposure estimation and evaluation of acute biological effects by in vitro inhalation were included to generate dose-response data, allowing for determination of in vitro lowest observable adverse effect levels (LOAELs). Correlation of these to estimates of human lung deposition was included for quantitative in vitro to in vivo extrapolation approach (QIVIVE) for acute effects during human exposure. METHODS: To test the proposed approach, a case study was undertaken using two realistic test materials. An acute in vitro inhalation setup with air-liquid interface A549-cells in an optimized exposure situation (P.R.I.T.® ExpoCube®) was used to expose cells and analysis of relevant biological effects (viability, mitochondrial membrane potential, stress, IL-8 release) was carried out. RESULTS: The observed dose-responsive effects in a sub-toxic dose-range could be attributed to the main component of one test material and its presence in the aerosol phase of the nebulized material. QIVIVE resulted in a factor of at least 256 between the in vitro LOAEL and the estimated acute human lung exposure for this test material. CONCLUSIONS: The case-study shows the value of the non-target in vitro inhalation testing approach especially in case of a lack of knowledge on complex product composition. It is expected that approaches like this will be of high value for product safety and environmental health in the future.

Design of a routine in vitro inhalation approach to estimate biological effects of nebulized products.Application in a case study on a potential real product for purposeful room conditioning by use of a commercial nebulizer.Combining results from aerosol characterization and in vitro inhalation experiments allowed for comprehensive correlation of product composition, aerosol properties and biological effects.Assignment of sub-toxic biological effects to a specific product component enabled identification of a product composition with potentially even less biological effect.Combined in vivo exposure estimation and in vitro LOAEL determination enabled a QIVIVE approach.

Headlines win elections: Mere exposure to fictitious news media alters voting behavior.

Repeatedly encountering a stimulus biases the observer's affective response and evaluation of the stimuli. Here we provide evidence for a causal link between mere exposure to fictitious news reports and subsequent voting behavior. In four pre-registered online experiments, participants browsed through newspaper webpages and were tacitly exposed to names of fictitious politicians. Exposure predicted voting behavior in a subsequent mock election, with a consistent preference for frequent over infrequent names, except when news items were decidedly negative. Follow-up analyses indicated that mere media presence fuels implicit personality theories regarding a candidate's vigor in political contexts. News outlets should therefore be mindful to cover political candidates as evenly as possible.

Sodium Chloride versus Lactose as a Carrier for House Dust Mite Allergen in Allergen Chamber Studies: A Clinical Study to Assess Noninferiority.

INTRODUCTION: In the Fraunhofer allergen challenge chamber (ACC), a standardized, universal, good manufacturing practice-conforming technology using a spray dried solution of lactose (L) and allergen extract has been established. In this study, we investigated the noninferiority of hypertonic sodium chloride (S) versus L as a carrier for house dust mite (HDM) allergen to simplify manufacturing, reduce costs, and allow for wider use. METHODS: Using a participant-blinded, sham exposure-controlled, single-arm, sequential intervention study, we challenged adults with HDM allergic rhinitis five times in the ACC. Participants were first exposed to S, L, and clean air (block 1), followed by S + HDM and L + HDM (block 2). Primary endpoints were mean total nasal symptom score (TNSS) and mean nasal secretion weight. RESULTS: 19 participants were enrolled in the study (10 females; mean age 32 years [22-49], 4 with mild allergic asthma). The safety profile of S + HDM and L + HDM was similar; eight participants experienced mild procedure-related adverse events including tiredness, cough, and dyspnea. Due to dropouts, 13 participants completed the study and were evaluated. Mean TNSS and nasal secretion were as follows: S 0.98, 0.28 g; L 1.1, 0.20 g; clean air 1.1, 0.23 g; S + HDM 5.7, 4.8 g; L + HDM 5.1, 5.1 g. Separate block 1/block 2 MANOVAs with TNSS and nasal secretion as dependent variables revealed no significant differences between the carriers, neither alone and compared with clean air (p = 0.2059, Wilk's λ = 0.78) nor combined with HDM (p = 0.3474, Wilk's λ = 0.89). Noninferiority of S was established using a meta-analysis-based minimal clinical important difference of -0.55: mean TNSS difference between S + HDM and L + HDM was 0.62 (90% CI: -0.51 to 1.74). CONCLUSION: S as an HDM carrier was safe and well tolerated. It was noninferior to L which makes it an adequate and easy-to-use carrier substitute.

Soil texture mediates the surface cooling effect of urban and peri-urban green spaces during a drought period in the city area of Hamburg (Germany).

Urban green spaces (UGS) and peri-urban green spaces (P-UGS) play a crucial role in reducing the land surface temperature within the urban environment, especially during heat waves. Although their cooling effect generally is due to shading and evaporation, the role of soil texture and soil water availability on surface cooling remains largely unexplored. This study investigated the impact of soil texture on the spatio-temporal patterns of LST in different UGSs and P-UGSs in Hamburg (Germany) during a hot summer drought period. The LST and the Normalized Differentiated Moisture and Vegetation Indices (NDMI, NDVI) were calculated based on two Landsat 8 OLI/TIRS images from July 2013. Non-spatial and spatial statistical approaches such as stepwise backward regression or Hotspot (Getis-Ord Gi*) analyses were applied explaining LST distributions in relation to soil texture within each UGS and P-UGS. All GSs were clearly characterized as surface cooling islands whereas, for each GS, an individual thermal footprint was observed. Within all GSs, the LST patterns showed a significant negative relationship to NDMI values, whereas the NDVI values and the elevation were of minor importance. Soil texture was found to influence the LST distribution significantly in most UGSs and P-UGSs, where sites on clay-rich soils showed the highest LST values compared to sites on sand- or silt-rich soils. For example, in parks, clayey soils showed a mean LST of 25.3 °C whereas sand-dominated sites had a mean LST of only 23.1 °C. This effect was consistent throughout all statistical approaches, for both dates and across most GSs. This unexpected result was explained by the very low unsaturated hydraulic conductivity in clayey soils which limits plant water uptake and transpiration rates responsible for the evaporative cooling effect. We concluded that soil texture has to be considered for understanding and managing the surface cooling capacity of UGSs and P-UGSs.

Inhalation and dermal exposure to biocidal products during foam and spray applications.

OBJECTIVES: Foaming and spraying are common application techniques for biocidal products. In the past, inhalation and dermal exposure during spraying have been investigated extensively. Currently, however, no exposure data are available for foaming, hindering a reliable risk assessment for foam applications of biocidal products. The focus of this project was the quantification of inhalation and potential dermal exposure to non-volatile active substances during the foam application of biocidal products in occupational settings. In some settings, exposure during spray application was measured for comparative purposes. METHODS: The inhalation and dermal exposure of operators were investigated during the application of benzalkonium chlorides and pyrethroids by foaming and spraying, considering both small- and large-scale application devices. Inhalation exposure was measured by personal air sampling; potential dermal exposure was measured using coveralls and gloves. RESULTS: Potential dermal exposure was substantially higher than inhalation exposure. Changing from spraying to foaming reduced inhalation exposure to airborne non-volatile active substances, but had no relevant effect on potential dermal exposure. However, for potential dermal exposure, considerable differences were observed between the application device categories. CONCLUSIONS: To our knowledge, this study presents the first comparative exposure data for the foam and spray application of biocidal products in occupational settings with detailed contextual information. The results indicate a reduction of inhalation exposure with foam application compared to spray application. However, special attention is necessary for dermal exposure, which is not reduced by this intervention.

Aerosol formation during foam application of non-volatile biocidal substances.

The application of biocidal products by foam is considered an alternative to droplet spraying when disinfecting surfaces or fighting infestations. Inhalation exposure to aerosols containing the biocidal substances cannot be ruled out during foaming. In contrast to droplet spraying, very little is known about aerosol source strength during foaming. In this study, the formation of inhalable aerosols was quantified according to the aerosol release fractions of the active substance. The aerosol release fraction is defined as the mass of active substance transferred into inhalable airborne particles during foaming, normalised to the total amount of active substance released through the foam nozzle. Aerosol release fractions were measured in control chamber experiments where common foaming technologies were operated according to their typical conditions of use. These investigations include foams generated mechanically by actively mixing air with a foaming liquid as well as systems that use a blowing agent for foam formation. The values of the aerosol release fraction ranged from 3.4 × 10-6 to 5.7 × 10-3 (average values). For foaming processes based on mixing air and the foaming liquid, the release fractions could be correlated to the process and foam parameters such as foam exit velocity, nozzle dimensions, and foam expansion ratio.

Amorphous Drug Nanoparticles for Inhalation Therapy of Multidrug-Resistant Tuberculosis.

Tuberculosis (TB) is one of the most prevalent infectious diseases. The global TB situation is further complicated by increasing patient numbers infected with Mycobacterium tuberculosis (M.tb.) strains resistant to either one or two of the first-line therapeutics, promoted by insufficient treatment length and/or drug levels due to adverse reactions and reduced patient compliance. An intriguing approach to improve anti-TB therapy relates to nanocarrier-based drug-delivery systems, which enhance local drug concentrations at infection sites without systemic toxicity. Recently developed anti-TB antibiotics, however, are lipophilic and difficult to transport in aqueous systems. Here, the very lipophilic TB-antibiotics bedaquiline (BDQ) and BTZ (1,3-benzothiazin-4-one 043) are prepared as high-dose, amorphous nanoparticles via a solvent-antisolvent technique. The nanoparticles exhibit mean diameters of 60 ± 13 nm (BDQ) and 62 ± 44 nm (BTZ) and have an extraordinarily high drug load with 69% BDQ and >99% BTZ of total nanoparticle mass plus a certain amount of surfactant (31% for BDQ, <1% for BTZ) to make the lipophilic drugs water-dispersible. Suspensions with high drug load (4.1 mg/mL BDQ, 4.2 mg/mL BTZ) are stable for several weeks. In vitro and in vivo studies employing M.tb.-infected macrophages and susceptible C3HeB/FeJ mice show promising activity, which outperforms conventional BDQ/BTZ solutions (in DMF or DMSO) with an up to 50% higher efficacy upon pulmonary delivery. In vitro, the BDQ/BTZ nanoparticles demonstrate their ability to cross the different biological barriers and to reach the site of the intracellular mycobacteria. In vivo, high amounts of the BDQ/BTZ nanoparticles are found in the lung and specifically inside granulomas, whereas only low BDQ/BTZ-nanoparticle levels are observed in spleen or liver. Thus, pulmonary delivered BDQ/BTZ nanoparticles are promising formulations to improve antituberculosis treatment.

Sense of agency in social hierarchies.

Distributing complex actions across agents is commonplace in human society. The objective efficiency of joint actions comes with critical challenges for the sense of agency of individual agents, complicating an accurate formation of these agents' perceived control over actions and action outcomes. Here we report a new experimental paradigm to investigate sense of agency for supervisors and subordinates in hierarchical settings. Results indicate profound differences in the sense of agency between both roles, while also indicating additional contributions of such situational factors as degrees of freedom, action decision versus action execution, outcome valence, and veto options. We further observed a tight coupling of sense of agency and sense of responsibility, with only weak links to affective responses to the action outcome. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Child and adolescent health in Europe: Towards meeting the 2030 agenda.

Background: Childhood and adolescence are critical stages for a healthy life. To support countries in promoting health and development and improving health care for this age group, the WHO Regional Office for Europe developed the European strategy for child and adolescent health 2015-2020, which was adopted by all countries. This paper reports progress in the strategy's implementation until 2020. Methods: A survey was sent to all ministries of health of the 53 Member States of the WHO European Region. Responses were received from 45 Member States. Results are presented in this paper. Results: The European Region made overall progress in recent years, but increasing levels of overweight and obesity among children, adolescent mental health and low breastfeeding rates are recognized as key national challenges. Although forty-one countries adopted a national child and adolescent health strategy, only eight countries involve children in their review, development and implementation stages. Two-thirds of countries have a strategy for health-promoting schools and a school curriculum for health education. One-third of countries do not have legislation against marketing of unhealthy foods and beverages to children. Most countries reported routine assessment for developmental difficulties in children, but less than a quarter collected and reported data on children who are developmentally on track. There are major gaps in data collection for migrant children. Hospitalization rates for young children vary five-fold across the region, indicating over-hospitalization and access problems in some countries. Only ten countries allow minors access to health care without parental consent based on their maturity and only eleven countries allow school nurses to dispense contraceptives to adolescents without a doctor's prescription. Conclusions: This paper shows the progress in child and adolescent health made by countries in Europe until 2020 and key areas where additional work is needed to move the 2030 agenda forward. The survey was undertaken before the COVID-19 pandemic and the war in Ukraine. Both will likely exacerbate many of the observed problems and potentially reverse some gains reported. A renewed commitment is needed.

Distracted to a fault: Attention, actions, and time perception.

In the last years, it has become general consensus that actions change our time perception. Performing an action to elicit a specific event seems to lead to a systematic underestimation of the interval between action and effect, a phenomenon termed temporal (or previously intentional) binding. Temporal binding has been closely associated with sense of agency, our perceived control over our actions and our environment, and because of its robust behavioral effects has indeed been widely utilized as an implicit correlate of sense of agency. The most robust and clear temporal binding effects are typically found via Libet clock paradigms. In the present study, we investigate a crucial methodological confound in these paradigms that provides an alternative explanation for temporal binding effects: a redirection of attentional resources in two-event sequences (as in classical operant conditions) versus singular events (as in classical baseline conditions). Our results indicate that binding effects in Libet clock paradigms may be based to a large degree on such attentional processes, irrespective of intention or action-effect sequences. Thus, these findings challenge many of the previously drawn conclusions and interpretations with regard to actions and time perception.

Never run a changing system: Action-effect contingency shapes prospective agency.

Human action control is highly sensitive to action-effect contingencies in the agent's environment. Here we show that the subjective sense of agency (SoA) contributes to this sensitivity as a subjective counterpart to instrumental action decisions. Participants (N = 556) experienced varying reward probabilities and were prompted to give summary evaluations of their SoA after a series of action-effect episodes. Results first revealed a quadratic relation of contingency and SoA, driven by a disproportionally strong impact of perfect action-effect contingencies. In addition to this strong situational determinant of SoA, we observed small but reliable interindividual differences as a function of gender, assertiveness, and neuroticism that applied especially at imperfect action-effect contingencies. Crucially, SoA not only reflected the reward structure of the environment but was also associated with the agent's future action decisions across situational and personal factors. These findings call for a paradigm shift in research on perceived agency, away from the retrospective assessment of single behavioral episodes and towards a prospective view that draws on statistical regularities of an agent's environment.

Error cancellation.

The human cognitive system houses efficient mechanisms to monitor ongoing actions. Upon detecting an erroneous course of action, these mechanisms are commonly assumed to adjust cognitive processing to mitigate the error's consequences and to prevent future action slips. Here, we demonstrate that error detection has far earlier consequences by feeding back directly onto ongoing motor activity, thus cancelling erroneous movements immediately. We tested this prediction of immediate auto-correction by analysing how the force of correct and erroneous keypress actions evolves over time while controlling for cognitive and biomechanical constraints relating to response time and the peak force of a movement. We conclude that the force profiles are indicative of active cancellation by showing indications of shorter response durations for errors already within the first 100 ms, i.e. between the onset and the peak of the response, a timescale that has previously been related solely to error detection. This effect increased in a late phase of responding, i.e. after response force peaked until its offset, further corroborating that it indeed reflects cancellation efforts instead of consequences of planning or initiating the error.

Exercise Improves Cognitive Function-A Randomized Trial on the Effects of Physical Activity on Cognition in Type 2 Diabetes Patients.

BACKGROUND: Lifestyle habits strongly influence health. It is strongly believed that physical activity may improve cognitive function. We examined the association between two kinds of physical activity and cognitive function in patients with type 2 diabetes. METHODS: Using a random allocation sequence, 49 patients with type 2 diabetes (metformin, insulin, and diet-controlled) were randomized to a 12-week intervention of either walking 40 min three times a week (n = 17), performing pedometer-controlled activity (E-health, goal 10,000 steps a day, n = 17), or receiving standard care (n = 16 controls). We prospectively examined cognitive function, metabolic parameters, height, and weight. The groups were compared using linear regression adjusted for age. RESULTS: Compared with the control group (n = 16), nonverbal memory improved significantly after the intervention in the walking group (n = 16) (28.2 (+/-6.1) vs. 35.3 (+/-5.3) p < 0.001) and the E-health (pedometer) group ((n = 17) (29.7 (+/-3.9) vs. 35.6 (+/-3.8) p < 0.001). The verbal memory test showed improvement in the walking and E-health groups. Cognitive attention/performance measured by the FAIR-test was also significantly enhanced in the walking group (252.4/304.3 p < 0.001, 51.87 (CI 27.13-76.62)) and the E-health-group (85.65 (CI: 52.04-119.26, p < 0.001)). Abdominal circumference (-3 cm (CI: -9.69-3.31, p < 0.001)), heart rate (-6.50 (CI: -9.69, -3.31, p < 0.001)) and fat percentage (-2.74 (CI: -4.71, -0.76, p < 0.007)) changed significantly in only the walking group. CONCLUSIONS: This is the first intervention study in patients with type 2 diabetes that shows that pedometer-supported training significantly improves brain function. Walking additionally improves body composition and waist circumference. Physical activity is an inexpensive treatment with substantial preventative and restorative properties for cognitive and memory brain function in patients with type 2 diabetes.

Prenatal developmental toxicity studies on fumes from oxidised asphalt (OA) in the rat.

The prenatal developmental toxicity of the fumes of oxidised asphalt (OA) was tested by nose-only inhalation in the rat. The test material was generated by collecting fumes from the headspace of storage tanks filled with OA. The composition of these fumes was matched to fumes sampled at a workplace where the same OA was applied in a pour-and-roll operation, representing occupational exposure with high concentrations of fumes to not underestimate the possible hazard. In the main study, dams were exposed to 0, 53, 158 and 536 mg/m3 of fume (as total organic mass), for 6 h/day for 19 days p.c. The maternal NOAEC was 53 mg/m³ (lowest dose tested). In the high-dose group treatment-related effects on body weight gain were seen. In the mid- and high-dose groups treatment-related effects on food consumption, lung weights, and histopathological changes in lungs and the upper respiratory tract were observed. The NOAEC for prenatal developmental toxicity was 536 mg/m³ since no exposure-related effects were found in any of the exposure groups for any of the investigated reproductive endpoints. Furthermore, nose-only exposure to OA fumes in concentrations up to 536 mg/m³ from days 1-19 p.c. did not induce any significant fetal abnormalities.

To prevent means to know: Explicit but no implicit agency for prevention behavior.

Human agents draw on a variety of explicit and implicit cues to construct a sense of agency for their actions and the effects of these actions on the outside world. Associative mechanisms binding actions to their immediate effects support the evolution of agency for operant actions. However, human agents often also act to prevent a certain event from occurring. Such prevention behavior poses a critical challenge for the sense of agency, as successful prevention inherently revolves around the absence of a perceivable effect. By assessing the psychological microstructure of singular operant and prevention actions we show that this comes with profound consequences: agency for prevention actions is only evident in explicit measures but not in corresponding implicit proxies. These findings attest to an altered action representation in prevention behavior and they support recent proposals to model related processes such as avoidance learning in terms of propositional rather than associative terms.

Prenatal developmental toxicity studies on fumes from bitumen in the rat.

The prenatal developmental toxicity of bitumen fume was tested by nose-only inhalation in the rat. The fumes for exposure were collected from the headspace of a storage tank filled with a bitumen corresponding in composition to an anticipated worst-case occupational exposure. The composition of these fumes was compared to actual paving site fumes to ensure its representativeness for workplace exposures. In a dose-range-finding study male and female rats were exposed to 0, 103, 480 or 1043 mg/m3 of fume (as total organic mass), for 6 h/day during 20 days post conception (p.c.). Dose-related effects on body weight and lungs were observed in the mid- and high-dose groups. In the main study, dams were exposed to 0, 52, 151 and 482 mg/m3 of fume, for 6 h/day during 19 days p.c. The maternal NOAEL was 52 mg/m³. In the high-dose group treatment-related effects on body weight (gain), food consumption, lung weights, and histopathological changes in lungs and larynx were observed. In the mid-dose group only histopathological changes in the larynx and lungs were found. The NOAEL for prenatal developmental toxicity was 151 mg/m³ based on reduced fetal weight in the high-dose group (482 mg/m³). However, these changes are most likely a consequence of the maternal toxicity, in particular the reduction of maternal body weight gain by 26 % as compared to control. Nose-only exposure to bitumen fumes in concentrations up to 482 mg/m³ from days 1-19 p.c. did not induce any significant fetal anomalies.

Short-Term Outcomes of Surgery for Graves' Disease in Germany.

BACKGROUND: Surgical treatment of Graves' disease (GD) has a potentially increased incidence of postoperative hypoparathyroidism, recurrent laryngeal nerve palsy (RLNP) and bleeding. The aim of this study was to evaluate the current extent of surgery for the treatment of GD and its safety as a short-term outcome. METHODS: Patients who underwent thyroid resection for GD were identified from the prospective StuDoQ/Thyroid registry. Patient data were retrospectively analyzed regarding demographics, surgical procedures and perioperative outcomes. Statistics were performed with Student's t-test or Fisher's exact test and multivariate Cox regression analysis. The level of statistical significance was set at p < 0.05. RESULTS: A total of 1808 patients with GD with a median age of 44 (range 14-85) years were enrolled in a 25-month period by 78 departments, of which 35.7% (n = 645) had an endocrine orbitopathy and 0.1% (n = 6) had thyrotoxic crisis. Conventional open surgery was used in 98.6% of cases and minimally invasive or remote-access approaches were used in 1.4%. Total thyroidectomy was performed in 93.4% of cases (n = 1688). Intraoperative neuromonitoring (IONM) was used in 98.9% (n = 1789) of procedures. In 98.3% (n = 1777) at least one parathyroid gland was visualized and in 20.7% (n = 375) parathyroids were autografted. The rates of unilateral and bilateral transient RLNP were 3.9% (n = 134/3429 nerves at risk) and 0.1% (n = 4/3429 NAR). The rates of transient RLNP tended to be higher when intermittent IONM was used compared to continuous IONM (4.1% vs. 3.4%, p < 0.059). The rate of transient postoperative hypoparathyroidism was overall 29% (n = 525/1808). Multivariate analysis revealed fewer than 300 thyroid resections and fewer than 15 thyroid resections for GD per year, male sex, BMI > 30, autotransplantation of parathyroid glands and previous bilateral thyroid surgery as independent risk factors for postoperative temporary hypoparathyroidism. Reoperations for bleeding (1.3%) were rare. CONCLUSION: Total thyroidectomy with IONM is safe and currently the most common surgical therapy for GD in Germany. Postoperative hypoparathyroidism is the major complication which should be focused on.

Potentials of using milk performance data and FAMACHA score as indicators for Targeted Selective Treatment in Lacaune dairy sheep in Switzerland.

Targeted Selective Treatment (TST) is one approach to slow down the development of anthelmintic resistance. Its success is closely linked to the correct identification of animals in need of treatment. In dairy goats it has been proposed to use milk yield as TST indicator and to focus treatments on high yielding dairy goats. In dairy sheep the relationship between milk performance and infection with gastrointestinal nematodes (GIN) is not well known. The aim of this study was to investigate the relationship between milk yield and GIN infection in dairy sheep and based on this, to evaluate milk performance data as a potential TST indicator. Overall 1159 Lacaune ewes of 15 dairy sheep farms in Switzerland were included in the study. The ewes were phenotyped once between August and December 2019, when they were at least 70 days in milk (DIM). Individual faecal samples were taken from every ewe to determine the nematode egg concentration per gram faeces (EPG). In addition, the clinical parameters FAMACHA score and packed cell volume (PCV) were measured. Linear mixed models were used to analyse the effects of the collected parameters on EPG. EPG increased significantly with increasing test day milk yields (P = 0.002), indicating high yielding ewes to be less resistant to GIN infections than low yielding ewes. The effect was most pronounced in earlier lactation but remained within a moderate range. Overall, our results indicated the potential of using milk yield data of rather early lactation as TST indicator in dairy sheep. On farms with predominantly H. contortus the combination with FAMACHA might improve the correct identification of highly infected ewes, as FAMACHA was correlated with EPG (r = 0.37, P < 0.001).