Enhancing Resilience in Biometric Research: Generation of 3D Synthetic Face Data Using Advanced 3D Character Creation Techniques from High-Fidelity Video Games and Animation.

Biometric authentication plays a vital role in various everyday applications with increasing demands for reliability and security. However, the use of real biometric data for research raises privacy concerns and data scarcity issues. A promising approach using synthetic biometric data to address the resulting unbalanced representation and bias, as well as the limited availability of diverse datasets for the development and evaluation of biometric systems, has emerged. Methods for a parameterized generation of highly realistic synthetic data are emerging and the necessary quality metrics to prove that synthetic data can compare to real data are open research tasks. The generation of 3D synthetic face data using game engines' capabilities of generating varied realistic virtual characters is explored as a possible alternative for generating synthetic face data while maintaining reproducibility and ground truth, as opposed to other creation methods. While synthetic data offer several benefits, including improved resilience against data privacy concerns, the limitations and challenges associated with their usage are addressed. Our work shows concurrent behavior in comparing semi-synthetic data as a digital representation of a real identity with their real datasets. Despite slight asymmetrical performance in comparison with a larger database of real samples, a promising performance in face data authentication is shown, which lays the foundation for further investigations with digital avatars and the creation and analysis of fully synthetic data. Future directions for improving synthetic biometric data generation and their impact on advancing biometrics research are discussed.

Customizable Presentation Attack Detection for Improved Resilience of Biometric Applications Using Near-Infrared Skin Detection.

Due to their user-friendliness and reliability, biometric systems have taken a central role in everyday digital identity management for all kinds of private, financial and governmental applications with increasing security requirements. A central security aspect of unsupervised biometric authentication systems is the presentation attack detection (PAD) mechanism, which defines the robustness to fake or altered biometric features. Artifacts like photos, artificial fingers, face masks and fake iris contact lenses are a general security threat for all biometric modalities. The Biometric Evaluation Center of the Institute of Safety and Security Research (ISF) at the University of Applied Sciences Bonn-Rhein-Sieg has specialized in the development of a near-infrared (NIR)-based contact-less detection technology that can distinguish between human skin and most artifact materials. This technology is highly adaptable and has already been successfully integrated into fingerprint scanners, face recognition devices and hand vein scanners. In this work, we introduce a cutting-edge, miniaturized near-infrared presentation attack detection (NIR-PAD) device. It includes an innovative signal processing chain and an integrated distance measurement feature to boost both reliability and resilience. We detail the device's modular configuration and conceptual decisions, highlighting its suitability as a versatile platform for sensor fusion and seamless integration into future biometric systems. This paper elucidates the technological foundations and conceptual framework of the NIR-PAD reference platform, alongside an exploration of its potential applications and prospective enhancements.

New insights into the characterization of the mechanism of action of hyoscine butylbromide in the human colon ex vivo.

INTRODUCTION: Hyoscine butylbromide (HBB) is one of the most used antispasmodics in clinical practice. Recent translational consensus has demonstrated a similarity between human colonic motor patterns studied ex vivo and in vivo, suggesting ex vivo can predict in vivo results. It is unclear whether the mechanism of action of antispasmodics can predict different use in clinical practice. The aim of the present study is to bridge this gap dissecting HBB's role in excitatory and inhibitory neural pathways. METHODS: 309 colon samples from 48 patients were studied in muscle bath experiments. HBB was tested on: 1-spontaneous phasic contractions (SPCs); 2-carbachol-induced contractility; electrical field stimulation (EFS)-induced selective stimulation of 3-excitatory and 4-inhibitory pathways and 5- SPCs and EFS-induced contractions enhanced by neostigmine. Atropine, AF-DX116 (M2 blocker) and DAU-5884 (M3 blocker) were used as comparators. RESULTS: In the presence of tetrodotoxin (TTX), HBB and atropine 1 µM reduced SPCs. HBB and atropine concentration-dependently reduced carbachol- and EFS-induced contractions. Inhibitory effects of DAU-5884 on EFS-induced contractions were more potent than of AF-DX116. HBB did not affect the off-response associated to neural inhibitory responses. Neostigmine enhanced both SPCs and EFS-induced contractions. In the presence of TTX and ω-conotoxin (GVIA), neostigmine still enhanced SPCs. Addition of HBB and atropine reduced these responses. CONCLUSIONS: This study demonstrates that HBB inhibits neural cholinergic contractions associated to muscarinic (mainly M3) receptors. HBB has a potential role in reducing colonic spasm induced by the release of acetylcholine from enteric motor neurons and from an atypical source including a potential non-neuronal origin.

Prevalence and patterns of laxative use in subjects with self-reported constipation: results from a multinational digestive health survey.

Background: Constipation is characterized by symptoms of straining, hard stool, difficult evacuation, and infrequent bowel movements. Online surveys provide valuable information about patients' perspectives, symptoms, management, treatment satisfaction, and risk factors. Methods: This survey explored subject experiences involving 20 gastrointestinal (GI) conditions. In total, 20,099 respondents in seven countries with varied cultural and socioeconomic backgrounds participated. Post hoc analysis of 'self-reported constipation' and related symptoms experienced within the past 6 months and the last episode of constipation provided data on prevalence, demographics, frequency and duration of episodes and related symptoms, impact on quality of life (QoL), management with or without laxatives, and resulting treatment satisfaction. Results: In total, 10,425 subjects reported constipation within 6 months and 2637 at the last episode. Prevalence was highest in females and younger adults. Most subjects reported various coexisting GI symptoms. Almost 80% of 6865 episodes reported by 5337 subjects occurred every 2-3 months to every 2-3 weeks. A higher frequency of constipation correlated with a greater impact on QoL. On a 10-point scale, the mean impact was 6.4. More than 90% of respondents had episodes ranging from 1 day to 1 week. More than 90% took action; 16% used laxatives, of whom 80.3% were satisfied. Conclusion: Constipation, a highly prevalent disorder, spans cultures and socioeconomic classes. Its chronic recurrence has a significant impact on QoL, resulting in symptom self-management in >90% of subjects. Significantly higher satisfaction rates in subjects treated with than without laxatives reflect subjects' reports that self-reported constipation can be treated effectively with laxatives.

Predicting Undesired Treatment Outcomes With Machine Learning in Mental Health Care: Multisite Study.

Background: Predicting which treatment will work for which patient in mental health care remains a challenge. Objective: The aim of this multisite study was 2-fold: (1) to predict patients' response to treatment in Dutch basic mental health care using commonly available data from routine care and (2) to compare the performance of these machine learning models across three different mental health care organizations in the Netherlands by using clinically interpretable models. Methods: Using anonymized data sets from three different mental health care organizations in the Netherlands (n=6452), we applied a least absolute shrinkage and selection operator regression 3 times to predict the treatment outcome. The algorithms were internally validated with cross-validation within each site and externally validated on the data from the other sites. Results: The performance of the algorithms, measured by the area under the curve of the internal validations as well as the corresponding external validations, ranged from 0.77 to 0.80. Conclusions: Machine learning models provide a robust and generalizable approach in automated risk signaling technology to identify cases at risk of poor treatment outcomes. The results of this study hold substantial implications for clinical practice by demonstrating that the performance of a model derived from one site is similar when applied to another site (ie, good external validation).

A Retrospective Real-World Observational Study Assessing the Evolution of Bisacodyl Prescriptions in Patients with Constipation During Long-Term Treatment.

BACKGROUND: Potential habituation could be a safety concern associated with the long-term use of bisacodyl in patients with constipation. OBJECTIVE: In this study, we evaluated whether patients with constipation who require long-term treatment with bisacodyl will remain on a stable dose when treated for ≥ 28 days. METHODS: In this retrospective, population-based, observational cohort study, electronic medical record data of adult patients with constipation between January 1, 2011, and December 31, 2019, were collected from The Health Improvement Network French database. Total bisacodyl exposure during the long-term (≥ 28 days) and follow-up (12 months) periods was evaluated. The primary endpoint was the dose change status of bisacodyl during the follow-up period from the initial dose in the long-term cohort. RESULTS: Out of 5725 bisacodyl users in the database, 218 patients qualified to be part of the long-term cohort. A total of 166 (76.1%), 37 (17%), and 15 (6.9%) patients were initiated on bisacodyl at 5, 7.5, and 10 mg, respectively. During the follow-up, most (94%) of the patients remained on the same dose as initially prescribed for the first year. In contrast, only seven (3.2%) patients had their dose increased (from the initial prescribed dose of 5 mg), and the remaining six (2.8%) patients decreased their dose (four patients from the 7.5 mg group and two from the 10 mg group). CONCLUSION: Bisacodyl can be prescribed at a stable dose for > 28 days as most patients remained on their initial prescribed dose during the follow-up period. No signs of habituation were observed in this real-world study.

Lack of Evidence for Blood Pressure Effects of Caffeine Added to Ibuprofen.

BACKGROUND: Caffeine enhances the efficacy of non-opioid analgesics. Data on the cardiovascular health effects of caffeine intake are controversial, and studies on the cardiovascular effects of medical caffeine use are lacking. OBJECTIVE: The study aims to explore the cardiovascular effects of an ibuprofen/caffeine combination in comparison to ibuprofen alone. METHODS: Secondary analysis of a previously reported bioequivalence study of a single dose of a fixed dose ibuprofen/caffeine combination (400/100 mg) vs. ibuprofen alone in a randomized, cross-over design in 36 healthy volunteers. Plasma catecholamines were analyzed to enhance mechanistic interpretation of the data. RESULTS: After exclusion of 10 protocol violators (pre-dosing intake of caffeine), vital signs were comparable over a 24-h period in the absence and presence of caffeine. Plasma catecholamine levels were also comparable. CONCLUSION: These data do not support the hypothesis that occasional intake of a small dose of caffeine as part of pain medication imposes a health risk due to vital sign changes. Based on the proven increase in efficacy, the addition of caffeine to non-opioid analgesics such as IBU has a favorable risk/benefit profile for occasional use.

Situating language register across the ages, languages, modalities, and cultural aspects: Evidence from complementary methods.

In the present review paper by members of the collaborative research center "Register: Language Users' Knowledge of Situational-Functional Variation" (CRC 1412), we assess the pervasiveness of register phenomena across different time periods, languages, modalities, and cultures. We define "register" as recurring variation in language use depending on the function of language and on the social situation. Informed by rich data, we aim to better understand and model the knowledge involved in situation- and function-based use of language register. In order to achieve this goal, we are using complementary methods and measures. In the review, we start by clarifying the concept of "register", by reviewing the state of the art, and by setting out our methods and modeling goals. Against this background, we discuss three key challenges, two at the methodological level and one at the theoretical level: (1) To better uncover registers in text and spoken corpora, we propose changes to established analytical approaches. (2) To tease apart between-subject variability from the linguistic variability at issue (intra-individual situation-based register variability), we use within-subject designs and the modeling of individuals' social, language, and educational background. (3) We highlight a gap in cognitive modeling, viz. modeling the mental representations of register (processing), and present our first attempts at filling this gap. We argue that the targeted use of multiple complementary methods and measures supports investigating the pervasiveness of register phenomena and yields comprehensive insights into the cross-methodological robustness of register-related language variability. These comprehensive insights in turn provide a solid foundation for associated cognitive modeling.

Trop-2 induces ADAM10-mediated cleavage of E-cadherin and drives EMT-less metastasis in colon cancer.

We recently reported that activation of Trop-2 through its cleavage at R87-T88 by ADAM10 underlies Trop-2-driven progression of colon cancer. However, the mechanism of action and pathological impact of Trop-2 in metastatic diffusion remain unexplored. Through searches for molecular determinants of cancer metastasis, we identified TROP2 as unique in its up-regulation across independent colon cancer metastasis models. Overexpression of wild-type Trop-2 in KM12SM human colon cancer cells increased liver metastasis rates in vivo in immunosuppressed mice. Metastatic growth was further enhanced by a tail-less, activated ΔcytoTrop-2 mutant, indicating the Trop-2 tail as a pivotal inhibitory signaling element. In primary tumors and metastases, transcriptome analysis showed no down-regulation of CDH1 by transcription factors for epithelial-to-mesenchymal transition, thus suggesting that the pro-metastatic activity of Trop-2 is through alternative mechanisms. Trop-2 can tightly interact with ADAM10. Here, Trop-2 bound E-cadherin and stimulated ADAM10-mediated proteolytic cleavage of E-cadherin intracellular domain. This induced detachment of E-cadherin from ß-actin, and loss of cell-cell adhesion, acquisition of invasive capability, and membrane-driven activation of ß-catenin signaling, which were further enhanced by the ΔcytoTrop-2 mutant. This Trop-2/E-cadherin/ß-catenin program led to anti-apoptotic signaling, increased cell migration, and enhanced cancer-cell survival. In patients with colon cancer, activation of this Trop-2-centered program led to significantly reduced relapse-free and overall survival, indicating a major impact on progression to metastatic disease. Recently, the anti-Trop-2 mAb Sacituzumab govitecan-hziy was shown to be active against metastatic breast cancer. Our findings define the key relevance of Trop-2 as a target in metastatic colon cancer.

Bisacodyl: A review of pharmacology and clinical evidence to guide use in clinical practice in patients with constipation.

BACKGROUND: Bisacodyl is a member of the diphenylmethane family and is considered to be a stimulant laxative. It has a dual prokinetic and secretory action and needs to be converted into the active metabolite bis-(p-hydroxyphenyl)-pyridyl-2-methane (BHPM) in the gut to achieve the desired laxative effect. Bisacodyl acts locally in the large bowel by directly enhancing the motility, reducing transit time, and increasing the water content of the stool. A recent network meta-analysis concluded that bisacodyl showed similar efficacy to prucalopride, lubiprostone, linaclotide, tegaserod, velusetrag, elobixibat, and sodium picosulfate for the primary endpoint of ≥3 complete spontaneous bowel movements (CSBM)/week and an increase of ≥1 CSBM/week over baseline. The meta-analysis also found that bisacodyl may be superior to the other laxatives for the secondary endpoint of change from baseline in the number of spontaneous bowel movements per week in patients with chronic constipation. This observation stimulated the authors to review the available literature on bisacodyl, which has been available on the market since the 1950 s. PURPOSE: The aim of the current review was to provide an overview of the historic background, structure, function, and mechanism of action of bisacodyl. Additionally, we discuss the important features and studies for bisacodyl to understand its peculiar characteristics and guide its use in clinical practice, but also stimulate research on open questions.

Peptide microarray-based analysis of antibody responses to SARS-CoV-2 identifies unique epitopes with potential for diagnostic test development.

Humoral immunity to the Severe Adult Respiratory Syndrome (SARS) Coronavirus (CoV)-2 is not fully understood yet but is a crucial factor of immune protection. The possibility of antibody cross-reactivity between SARS-CoV-2 and other human coronaviruses (HCoVs) would have important implications for immune protection but also for the development of specific diagnostic ELISA tests. Using peptide microarrays, n = 24 patient samples and n = 12 control samples were screened for antibodies against the entire SARS-CoV-2 proteome as well as the Spike (S), Nucleocapsid (N), VME1 (V), R1ab, and Protein 3a (AP3A) of the HCoV strains SARS, MERS, OC43, and 229E. While widespread cross-reactivity was revealed across several immunodominant regions of S and N, IgG binding to several SARS-CoV-2-derived peptides provided statistically significant discrimination between COVID-19 patients and controls. Selected target peptides may serve as capture antigens for future, highly COVID-19-specific diagnostic antibody tests.

A novel digital approach to describe real world outcomes among patients with constipation.

Understanding day-to-day variations in symptoms and medication management can be important in describing patient centered outcomes for people with constipation. Patient Generated Health Data (PGHD) from digital devices is a potential solution, but its utility as a tool for describing experiences of people with frequent constipation is unknown. We conducted a virtual, 16-week prospective study of individuals with frequent constipation from an online wellness platform that connects mobile consumer digital devices including wearable monitors capable of passively collecting steps, sleep, and heart rate data. Participants wore a Fitbit monitoring device for the study duration and were administered daily and monthly surveys assessing constipation symptom severity and medication usage. A set of 38 predetermined day-level behavioral activity metrics were computed from minute-level data streams for steps, sleep and heart rate. Mixed effects regression models were used to compare activity metrics between constipation status (irregular or constipated vs. regular day), medication use (medication day vs. non-medication day) and the interaction of medication day with irregular or constipation days, as well as to model likelihood to treat with constipation medications based on daily self-reported symptom severity. Correction for multiple comparisons was performed with the Benjamini-Hochberg procedure for false discovery rate. This study analyzed 1540 enrolled participants with completed daily surveys (mean age 36.6 sd 10.0, 72.8% female, 88.8% Caucasian). Of those, 1293 completed all monthly surveys and 756 had sufficient Fitbit data density for analysis of activity metrics. At a daily-level, 22 of the 38 activity metrics were significantly associated with bowel movement or medication treatment patterns for constipation. Participants were measured to have fewer steps on irregular days compared to regular days (-200 steps, 95% CI [-280, -120]), longer periods of inactivity on constipated days (9.1 min, 95% CI [5.2, 12.9]), reduced total sleep time on irregular and constipated days (-2.4 min, 95% CI [-4.3, -0.4] and -4.0 min, 95% CI [-6.5, -1.4], respectively). Participants reported greater severity of symptoms for bloating, hard stool, difficulty passing, and painful bowel movements on irregular, constipation and medication days compared to regular days with no medication. Interaction analysis of medication days with irregular or constipation days observed small increases in severity compared to non-medication days. Participants were 4.3% (95% CI 3.2, 5.3) more likely to treat with medication on constipated days versus regular. No significant increase in likelihood was observed for irregular days. Daily likelihood to treat increased for each 1-point change in symptom severity of bloating (2.4%, 95% CI [2.0, 2.7]), inability to pass (2.2%, 95% CI [1.4, 3.0]) and incomplete bowel movements (1.3%, 95% CI [0.9, 1.7]). This is the first large scale virtual prospective study describing the association between passively collected PGHD and constipation symptoms and severity at a day-to-day granularity level. Constipation status, irregular or constipated, was associated with a number of activity metrics in steps and sleep, and likelihood to treat with medication increased with increasing severity for a number of constipation symptoms. Given the small magnitude of effect, further research is needed to understand the clinical relevance of these results. PGHD may be useful as a tool for describing real world patient centered experiences for people with constipation.

Neural surprise in somatosensory Bayesian learning.

Tracking statistical regularities of the environment is important for shaping human behavior and perception. Evidence suggests that the brain learns environmental dependencies using Bayesian principles. However, much remains unknown about the employed algorithms, for somesthesis in particular. Here, we describe the cortical dynamics of the somatosensory learning system to investigate both the form of the generative model as well as its neural surprise signatures. Specifically, we recorded EEG data from 40 participants subjected to a somatosensory roving-stimulus paradigm and performed single-trial modeling across peri-stimulus time in both sensor and source space. Our Bayesian model selection procedure indicates that evoked potentials are best described by a non-hierarchical learning model that tracks transitions between observations using leaky integration. From around 70ms post-stimulus onset, secondary somatosensory cortices are found to represent confidence-corrected surprise as a measure of model inadequacy. Indications of Bayesian surprise encoding, reflecting model updating, are found in primary somatosensory cortex from around 140ms. This dissociation is compatible with the idea that early surprise signals may control subsequent model update rates. In sum, our findings support the hypothesis that early somatosensory processing reflects Bayesian perceptual learning and contribute to an understanding of its underlying mechanisms.

The Impact of Baseline Pain Intensity on the Analgesic Efficacy of Ibuprofen/Caffeine in Patients with Acute Postoperative Dental Pain: Post Hoc Subgroup Analysis of a Randomised Controlled Trial.

INTRODUCTION: A fixed dose combination (FDC) of ibuprofen 400 mg and caffeine 100 mg has been shown to be more effective than ibuprofen 400 mg alone for the treatment of acute postoperative dental pain in a phase III randomised controlled trial. A post hoc subgroup analysis of the primary data from an active-/placebo-controlled, double-blind, single-centre, parallel-group study was conducted in patients with moderate or severe baseline pain. METHODS: After dental surgery, patients with moderate or severe pain, which was determined on a 4-point verbal rating scale ('no pain' to 'severe pain'), received a single dose of ibuprofen 400 mg/caffeine 100 mg FDC, ibuprofen 400 mg, caffeine 100 mg or placebo. Pain relief (PAR) and pain intensity were assessed 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7 and 8 h after administration of study medication. The primary study endpoint was the time-weighted sum of PAR and pain intensity difference (PID) from pre-dose baseline, summed for all post-dose assessment times from 0 to 8 h (SPRID0-8h). RESULTS: There were 237 patients with moderate pain and 325 with severe pain at baseline. SPRID0-8h was significantly improved with the FDC versus ibuprofen, caffeine and placebo in the moderate and severe pain subgroups. Adjusted mean SPRID0-8h difference for the FDC versus ibuprofen was 18.19 (p < 0.0001) for patients with moderate pain and 7.70 (p = 0.0409) for patients with severe pain. With the exception of the 7-h measurement in patients with moderate pain, PID was significantly improved with the FDC versus ibuprofen at all measured time points from 0.5 to 8 h. In the severe pain subgroup, PID was significantly improved for the FDC versus ibuprofen from 0.5 to 3 h post-dose, but was not significantly different thereafter. CONCLUSION: The enhanced analgesic efficacy of ibuprofen/caffeine FDC versus ibuprofen is most pronounced in patients with moderate intensity pain at baseline, and also evident in patients with severe baseline pain. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01929031.

The non-steroidal anti-inflammatory drug (NSAID) ibuprofen is commonly used to relieve mild to moderate pain. Research suggests that combining ibuprofen with caffeine can increase the analgesic efficacy. Previously, a randomised, double-blind, placebo-controlled study showed that this ibuprofen/caffeine combination was significantly more effective than ibuprofen alone for relieving pain after dental surgery (wisdom tooth removal). Patients in that study had moderate or severe pain, so the researchers conducted another analysis of the study data to investigate how well the ibuprofen/caffeine combination worked in patients with moderate pain and in patients with severe pain. The study found that a single dose of ibuprofen/caffeine was significantly more effective than ibuprofen alone in patients with moderate pain and in those with severe pain. The analgesic effects of ibuprofen/caffeine were more marked in patients with moderate pain than in those with severe pain. This indicates that ibuprofen/caffeine is an effective pain reliever for patients with moderate pain, and to a lesser extent in patients with severe pain.

Efficacy and Safety of Diclofenac + Capsaicin Gel in Patients with Acute Back/Neck Pain: A Multicenter Randomized Controlled Study.

INTRODUCTION: Back and neck pain are common musculoskeletal disorders. Topical non-steroidal anti-inflammatory drugs (NSAIDs) are frequently used to reduce pain and inflammation with fewer systemic side effects and drug interactions compared with oral NSAIDs. This study assessed efficacy and tolerability of a topical combination of capsaicin + diclofenac to treat acute back/neck pain. METHODS: In a randomized, double-blind, controlled, multicenter, parallel group trial, 746 patients were treated twice-daily for 5 days with diclofenac 2% + capsaicin 0.075%, diclofenac 2%, capsaicin 0.075% or placebo. Efficacy assessments included change and area under the curve in pain on movement for the worst procedure (POMWP), change in pressure algometry, and number of patients with decrease in POMWP of ≥ 30% and ≥ 50%. Adverse events (AEs) were recorded. RESULTS: Change in POMWP between baseline and day 2 evening, 1 h after drug application, demonstrates superiority of the combination (- 3.05 cm) versus diclofenac alone (- 2.33 cm) and placebo (- 2.45 cm), but not capsaicin alone (- 3.26 cm). AEs were consistent with known safety profiles. CONCLUSION: Capsaicin alone and capsaicin + diclofenac showed superior benefit compared with placebo. However, diclofenac alone demonstrated efficacy comparable with placebo, and therefore its addition to capsaicin added no increased pain relief over capsaicin alone. TRIAL REGISTRATION: ClinicalTrials.gov identifier; NCT02700815.

A randomized, placebo- and active-controlled, multi-country, multi-center parallel group trial to evaluate the efficacy and safety of a fixed-dose combination of 400 mg ibuprofen and 100 mg caffeine compared with ibuprofen 400 mg and placebo in patients with acute lower back or neck pain.

BACKGROUND: Ibuprofen is a well-established analgesic for acute pain symptoms. In several acute pain models, caffeine has demonstrated an analgesic adjuvant effect. This randomized trial (NCT03003000) was designed to compare the efficacy of a fixed-dose combination of ibuprofen and caffeine with ibuprofen or placebo for the treatment of acute lower back/neck pain. METHODS: Patients with acute lower back/neck pain resulting in pain on movement (POM) ≥5 on a 10-point numerical rating scale were randomized 2:2:1 to receive orally, three times daily for 6 days, 400 mg ibuprofen+100 mg caffeine, 400 mg ibuprofen or placebo, respectively. The primary endpoint was change in POMWP (POM triggering highest pain score at baseline [worst procedure]) between baseline and the morning of day 2. Key secondary endpoints included POMWP area under curve (AUC) between baseline and the morning of day 4 (POMWPAUC72h) and day 6 (POMWPAUC120h). RESULTS: In total, 635 patients were randomized (256 ibuprofen + caffeine: 253 ibuprofen: 126 placebo). Active treatments exhibited similar reductions in POMWP, with an adjusted mean reduction of 1.998 (standard error [SE]: 0.1042) between baseline and day 2 for ibuprofen, 1.869 (SE: 0.1030) for ibuprofen + caffeine and 1.712 (SE: 0.1422) for placebo. Similar results were observed for POMWPAUC72h and POMWPAUC120h. Safety and tolerability was as expected. CONCLUSION: A decrease in lower back/neck pain, indicated by reduced POMWP, was shown in all active treatment arms; however, treatment effects were small versus placebo. Ibuprofen plus caffeine was not superior to ibuprofen alone or placebo for the treatment of acute lower back/neck pain in this setting.

Biogenic Sources of Ice Nucleating Particles at the High Arctic Site Villum Research Station.

The radiative balance in the Arctic region is sensitive to in-cloud processes, which principally depend on atmospheric aerosols, including ice nucleating particles (INPs). High temperature INPs (active at ≥-15 °C) are common in the Arctic. While laboratory and limited in situ studies show that the high-temperature active INPs are associated with bioaerosols and biogenic compounds, there is still little quantitative insight into the Arctic biogenic INPs and bioaerosols. We measured concentrations of bioaerosols, bacteria, and biogenic INPs at the Villum Research Station (VRS, Station Nord) in a large number of snow (15) and air (51) samples. We found that INPs active at high subzero temperatures were present both in spring and summer. Air INP concentrations were higher in summer (18 INP m-3 at ≥-10 °C) than in spring (<4 INP m-3 at ≥-10 °C), when abundant INPs were found in snowfall (1.4 INP mL-1 at ≥-10 °C). Also, in summer, a significantly higher number of microbial and bacterial cells were present compared to the spring. A large proportion (60%-100%) of INPs that were active between -6 °C and -20 °C could be deactivated by heating to 100 °C, which was indicative of their predominantly proteinaceous origin. In addition, there was a significant linear regression between the summer air concentrations of INPs active at ≥-10 °C and air concentrations of bacterial-marker-genes (p < 0.0001, R2 = 0.999, n = 6), pointing at bacterial cells as the source of high-temperature active INPs. In conclusion, the majority of INPs was of proteinaceous, and possibly of bacterial, origin and was found in air during summer and in snowfall during springtime.

Pharmacokinetic Properties of Ibuprofen (IBU) From the Fixed-Dose Combination IBU/Caffeine (400/100 mg; FDC) in Comparison With 400 mg IBU as Acid or Lysinate Under Fasted and Fed Conditions-Data From 2 Single-Center, Single-Dose, Randomized Crossover Studies in Healthy Volunteers.

Rapid onset of analgesic action is linked with rapid absorption of analgesics (high maximum concentration [Cmax ] and short time to maximum concentration [tmax ]). After overnight fasting, ibuprofen lysinate reaches higher peak plasma levels (Cmax ) earlier than ibuprofen acid (tmax ) with comparable exposure (area under the plasma concentration-time curve [AUC]); however, subjects usually take ibuprofen with or within a short time of a meal. Therefore, pharmacokinetic (PK) studies under fed conditions may better characterize properties under real-life conditions. We investigated a new fixed-dose combination (FDC) of ibuprofen acid 400 mg and caffeine 100 mg in 2 single-dose, randomized, crossover PK studies in healthy subjects (both N = 36). The FDC was compared with ibuprofen 400 mg as acid and as lysinate after an overnight fast in Study 1, and with ibuprofen lysinate after a meal in Study 2. After fasting, results for ibuprofen in the FDC were comparable with those from ibuprofen acid alone. Caffeine did not affect the Cmax , tmax , and AUC. As expected, a higher Cmax and shorter tmax were observed with ibuprofen lysinates vs the FDC. Compared with administration after fasting, Cmax and tmax for ibuprofen lysinate administered postprandially were markedly different, while with FDC, these parameters were less sensitive to food intake. Taken after a meal, ibuprofen in the FDC reached tmax earlier than ibuprofen lysinate (median 1.25 vs 1.63 hours), and Cmax was approximately 13% higher, with comparable AUC, suggesting that the profile of ibuprofen was in favor of the FDC compared with ibuprofen lysinate. Thus, under real-life conditions, ibuprofen lysinate had no PK advantage over the FDC. All preparations were well tolerated.