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Format ties, “partial repetitions of prior talk” (Goodwin & Goodwin 1987, p. 207), are interesting from an interactional perspective with respect to their functions relating to, for example, (dis-) agreement/alignment or humour, and for scholars of Language Variation and Change because they offer uniquely comparable phonological contexts in naturalistic speech. The present paper investigates the distribution of the sociolinguistic variable ing in format ties in a set of dyadic interviews of six speakers from the North-East of England who were recorded two or three times throughout their twenties – those career-building years during which we often see a change from the predominant use of the alveolar variant (“in’”) to the velar (“ing”). The analysis offers possible interactional and stylistic explanations for the community-level stability and the speaker-level variation and change of ing by focusing on contexts in which speakers format tie. It shows that the use of the highly frequent and thus less marked alveolar variant tends to occur in aligning contexts, while the few velar cases occur in moments where speakers disalign on some level. This argument contributes to work combining interactional and variationist endeavours, in particular with respect to the variable ing.

Background: Microdialysis sampling after drug microdosing may provide tissue pharmacokinetic data early in clinical drug development. However, low administered doses and small sample volumes pose an analytical challenge, particularly for highly protein-bound drugs. Materials & methods: Carbon-14 [14C]diclofenac was used as a model drug to assess the technical and analytical feasibility of in vivo microdialysis after microdose administration in an in vitro setup. Results: [14C]diclofenac dialysate concentrations were accurately quantified with accelerator MS. [14C]diclofenac dialysate recoveries were similar in the presence and absence of therapeutic diclofenac concentrations but were considerably decreased when albumin was added to the immersion solution, suggesting high protein binding. Conclusion: These results demonstrate the feasibility of combining microdosing and microdialysis to assess tissue pharmacokinetics.

Purpose Clinical research relies on data from patients and volunteers, yet the target sample size is often not achieved. Here, we assessed the perception of clinical research among clinical trial participants to improve the recruitment process for future studies. Methods We conducted a single-center descriptive and exploratory study of 300 current or former participants in various phase I–III clinical trials. Questionnaires were either distributed to current clinical trial participants or emailed to former subjects. Results Subjects strongly agreed or agreed that contributing to improving medical care (> 81%), contributing to scientific research (> 79%), and trusting their treating physicians (> 77%) were motives for study participation. Among healthy volunteers, financial motives positively correlated with the number of clinical trials they had participated in (p p Conclusion Altruistic motives and trust in treating physicians were predominant motives for clinical trial participation. Older patients expected to receive the best available treatment during participation. Healthy volunteers who reported financial motives had participated in more clinical trials. Consistent with great trust in medical staff and government research institutions, little concern was expressed about the misuse of personal data during the trial.

To investigate immunogenicity and safety of BNT162b2 booster vaccination with and without a tetravalent influenza vaccine.A prospective, open-label cohort study on immunogenicity and safety of COVID-19 booster vaccination with or without a tetravalent influenza vaccine was performed. 838 health care workers were included in the following study arms: BNT162b2 booster-only, influenza-vaccine-only or combination of both. Levels of antibodies against SARS-CoV-2 spike receptor binding domain (RBD), and haemagglutinine inhibition (HAI) tested for four different influenza strains (A(H1N1)pdm09, A(H3N2), B/Victoria, B/Yamagata) were measured at time of vaccination and four weeks later.After four weeks, median [IQR] anti-RBD antibody levels and relative change from baseline were higher in individuals who received BNTb162b2 booster vaccination only (absolute: 16,600 [10,980-24,360] vs. 12,630 [8,198-18,750] BAU/mL (p0·0001); relative increase: 49% [23·6-95·3] vs. 40% [21·9-80·6](p = 0·048); booster-only n=521 vs. combination-arm n=229 respectively). Results were confirmed after matching for sex, age, BMI, baseline antibody levels and vaccine compound received for primary immunization (absolute: 13,930 [10,610 - 22,760] vs. 12,520 [8,710 - 17,940]; p = 0·031); relative increase: 55·7% [27·8-98·5] vs. 42·2% [22·9-74·5]; p = 0·045). Adverse events were almost identical in the booster-only and the combination-arm, but numerically lower in the influenza arm (525/536[97·9] % vs.235/240 [97·9%] vs. 26/33 [78·8 %]).While no safety concerns occurred, our study provides evidence on reduced immunogenicity of a BNT162b2 booster vaccination in combination with a tetravalent influenza vaccine. Further studies investigating new influenza variants as well as potential differences vaccine effectiveness are needed.

Spider silk has fascinated mankind for millennia, but it is only in recent decades that scientific research has begun to unravel all its characteristics and applications. The uniqueness of spider silk resides in its versatility, in which a combination of high strength and extensibility results in extraordinary toughness, superior to almost all natural and man-made fibers. Dragline silk consists of proteins with highly repetitive amino acid sequences, which have been correlated with specific secondary structures responsible for its physical properties. The native fiber also shows high cytocompatibility coupled with low immunogenicity, making it a promising natural biomaterial for numerous biomedical applications. Recently, novel technologies have enabled new insights into the material and biomedical properties of silk. Due to the increasing interest in spider silk, as well as the desire to produce synthetic alternatives, we present an update on the current knowledge of silk fibers produced by the spider genus Trichonephila.

Binding studies using the enantiomers of the synthetic cannabinoid 7-hydroxy-delta 6-tetrahydrocannabinol 1,1-dimethylheptyl homolog in preparations of rat brain cortical membranes reveal that the (+)-(3S,4S) enantiomer HU-211 blocks N-methyl-D-aspartate (NMDA) receptors in a stereospecific manner and that the interaction occurs at binding sites distinct from those of other noncompetitive NMDA antagonists or of glutamate and glycine. Moreover, HU-211 induces stereotype and locomotor hyperactivity in mice and tachycardia in rat, effects typically caused by NMDA receptor antagonists. HU-211 is also a potent blocker of NMDA-induced tremor, seizures, and lethality in mice. This compound may therefore prove useful as a nonpsychoactive drug that protects against NMDA-receptor-mediated neurotoxicity.

1 Implantation of morphine into various parts of the corpus striatum of rats evokes only weak gnawing responses. 2 Deposition of apomorphine, morphine or methadone in the region of the nucleus ventralis thalami produces a biphasic response, i.e. general excitation, followed by a period of intense gnawing. 3 The effect of both apomorphine and morphine is blocked by chlorpromazine, haloperidol and pimozide. However, pretreatment with α-methyltyrosine methyl ester or α-methyldopa prevents only the gnawing response to morphine, but not to apomorphine. 4 Systemic nalorphine, morphine or pethidine suppress the gnawing response, evoked by thalamic implants of apomorphine or morphine. 5 Systemic amphetamine potentiates the effect of thalamic deposits of morphine. 6 Compulsive gnawing, following implantation of morphine into the ventral region of the thalamus, probably results from enhanced production and release of catecholamines.

2-Chloropurine is attacked by mammalian xanthine oxidase simultaneously at C-6 and C-8. The ratio of the two rates (=1) is insensitive to variations of pH or temperature. Experiments with 2-chloropurine as inhibitor indicate instantaneous association of this purine with the active center of the enzyme. It is concluded that the rate-determining step, viz., conversion of ES → (ES)∗, is common to both pathways and that only in the subsequent interaction with water does the route fork.

The purified extract of a new bacterial mutant, which exhibits antibiotic activity against paramecia and amoebae, was tested on various smooth muscle preparations. Spontaneous activity as well as the response to a variety of smooth muscle stimulants was diminished or completely suppressed. Intravenous injection of the extract lowered the blood pressure of the anaesthetized cat or dog. These properties may explain the beneficial effect of the extract on the intestinal symptoms of human amoebiasis, before eradication of the parasites.

Nitroparaffins act on the guinea-pig ileum by several mechanisms. They produce contraction partly by ganglionic stimulation and partly by direct liberation of transmitter from the nerve endings. They also inhibit the response to acetylcholine and nicotine, but interfere less with the action of histamine, serotonin or bradykinin. The two opposite effects of the nitro compounds are independent of each other. Within the homologous series of normal nitroparaffins, the excitatory action diminishes and the inhibitory effect increases with the lengthening of the carbon chain.

Staphylococcus beta-haemolysin exhibits the same broad spectrum of antagonistic activity against smooth muscle stimulants as described recently for Colisan. The antispasmodic effect develops slowly and can be removed only by repeated washing. The pattern of haemolytic activities of Colisan is characteristically different from that of beta-haemolysin, but resembles closely alpha-toxin. Both staphylococcus toxins can destroy paramecium and entamoeba, but the ratio of the titres at which they kill paramecium and entamoeba respectively (P:A value) is different. The P:A value of beta-haemolysin is similar to that of Colisan.

SUMMARY: Although staphylococcal β-haemolysin does not lyse rabbit erythrocytes, it is absorbed by these cells and produces a prelytic change which can be recognized by facilitation of other haemolytic reactions. Combination of two haemolytic processes serves in general to detect latent effects of lytic agents or to accelerate their quantitative evaluation. β-Haemolysin apparently causes the same primary change in sheep and rabbit erythrocytes, namely enzymic splitting of sphingomyelin and related compounds, but only the sheep cells, when subjected to cooling, are able to undergo a second reaction, responsible for the release of haemoglobin.

Purified Colisan produces instantaneous lysis of paramecia and amoebae, and blebbing of paramecia, rat mast cells and ascites tumour cells. Colisan liberates histamine from mast cells. It also suppresses competitively the bradykinin-provoked contraction of the guinea-pig ileum. Most of these effects are not shared by staphylococcus-haemolysin. The results suggest a rapid change of the permeability of the cell membrane as the mechanism of all the diversified biological actions of Colisan.