The Impact of Point-of-Care Blood C-Reactive Protein Testing on Prescribing Antibiotics in Out-of-Hours Primary Care: A Mixed Methods Evaluation.

Improving prescribing antibiotics appropriately for respiratory infections in primary care is an antimicrobial stewardship priority. There is limited evidence to support interventions to reduce prescribing antibiotics in out-of-hours (OOH) primary care. Herein, we report a service innovation where point-of-care C-Reactive Protein (CRP) machines were introduced to three out-of-hours primary care clinical bases in England from August 2018-December 2019, which were compared with four control bases that did not have point-of-care CRP testing. We undertook a mixed-method evaluation, including a comparative interrupted time series analysis to compare monthly antibiotic prescription rates between bases with CRP machines and those without, an analysis of the number of and reasons for the tests performed, and qualitative interviews with clinicians. Antibiotic prescription rates declined during follow-up, but with no clear difference between the two groups of out-of-hours practices. A single base contributed 217 of the 248 CRP tests performed. Clinicians reported that the tests supported decision making and communication about not prescribing antibiotics, where having 'objective' numbers were helpful in navigating non-prescribing decisions and highlighted the challenges of training a fluctuant staff group and practical concerns about using the CRP machine. Service improvements to reduce prescribing antibiotics in out-of-hours primary care need to be developed with an understanding of the needs and context of this service.

Converging Evidence of Ubiquitous Male Bias in Human Sex Perception.

Visually judging the sex of another can be achieved easily in most social encounters. When the signals that inform such judgements are weak (e.g. outdoors at night), observers tend to expect the presence of males-an expectation that may facilitate survival-critical decisions under uncertainty. The present aim was to examine whether this male bias depends on expertise. To that end, Caucasian and Asian observers targeted female and male hand images that were either the same or different to the observers' race (i.e. long term experience was varied) while concurrently, the proportion of targets changed across presentation blocks (i.e. short term experience change). It was thus found that: (i) observers of own-race stimuli were more likely to report the presence of males and absence of females, however (ii) observers of other-race stimuli--while still tending to accept stimuli as male--were not prone to rejecting female cues. Finally, (iii) male-biased measures did not track the relative frequency of targets or lures, disputing the notion that male bias derives from prior expectation about the number of male exemplars in a set. Findings are discussed in concert with the pan-stimulus model of human sex perception.

Abnormalities in brain biochemistry associated with lack of dystrophin: studies of the mdx mouse.

Biochemical abnormalities have been reported in dystrophin-deficient muscle of boys with Duchenne (severe Xp21) muscular dystrophy or in the murine (mdx) model of the disease. These abnormalities include altered energy metabolism and responses to osmotic shock. In contrast, the situation in brain is less well understood and it is probable that dystrophin is playing a different role (or roles) in this organ. In this study we conclude that the elevation in choline-containing compounds reported in mdx brain is confined to cerebellum and hippocampus in older (> 6 months) mice. We report alterations in glucose metabolism in mdx brain under normal, awake conditions, and a reduced response of brain metabolism to the gamma-aminobutyric acid(A) receptor agonist muscimol. Using brain cortical slices we found no difference in the response of dystrophic tissue to hypoosmotic shock, but increased, substrate-dependent oxygen consumption rates at low oxygen partial pressures.

Differential sensitivity to calcium and osmotic pressure of fast and slow ATP currents at sympathetic varicosities in mouse vas deferens.

Secretion of noradrenaline from large dense-core vesicles in chromaffin cells involves both rapid and slow components of exocytosis which are differentially sensitive to changes in external calcium, osmotic pressure and interruption of the interacting SNARE proteins. Electrical signs of secretion of ATP from sympathetic nerve terminals of mouse vas deferens, the excitatory junctional currents (EJCs), also indicate both rapid and slow mechanisms of exocytosis, which might also show such differential sensitivity. We report here that the large and fast EJCs are highly sensitive to changes in extracellular calcium ions whereas the small and slow EJCs are not. Furthermore, the frequency of fast EJCs is accelerated by hypotonic solutions whereas the slow EJCs are accelerated by hypertonic solution. Fast EJCs, but not slow EJCs, are blocked by peptide fragments of alpha-SNAP and syntaxin whereas slow EJCs are not. These observations point to two classes of exocytosis from sympathetic nerve terminals that parallel those of exocytosis from chromaffin cells.

Hands as sex cues: sensitivity measures, male bias measures, and implications for sex perception mechanisms.

Sex perceptions, or more particularly, sex discriminations and sex categorisations, are high-value social behaviours. They mediate almost all inter-personal interactions. The two experiments reported here had the aim of exploring some of the basic characteristics of the processes giving rise to sex perceptions. Experiment 1 confirmed that human hands can be used as a cue to an individual's sex even when colour and texture cues are removed and presentations are brief. Experiment 1 also showed that when hands are sexually ambiguous observers tend to classify them as male more often than female. Experiment 2 showed that "male bias" arises not from sensitivity differences but from differences in response biases. Observers are conservative in their judgements of targets as female but liberal in their judgements of targets as male. These data, combined with earlier reports, suggest the existence of a sex-perception space that is cue-invariant.

Seeing the world topsy-turvy: The primary role of kinematics in biological motion inversion effects.

Physical inversion of whole or partial human body representations typically has catastrophic consequences on the observer's ability to perform visual processing tasks. Explanations usually focus on the effects of inversion on the visual system's ability to exploit configural or structural relationships, but more recently have also implicated motion or kinematic cue processing. Here, we systematically tested the role of both on perceptions of sex from upright and inverted point-light walkers. Our data suggest that inversion results in systematic degradations of the processing of kinematic cues. Specifically and intriguingly, they reveal sex-based kinematic differences: Kinematics characteristic of females generally are resistant to inversion effects, while those of males drive systematic sex misperceptions. Implications of the findings are discussed.

Impact of laboratory accreditation on patient care and the health system.

Accreditation is emerging as a preferred framework for building quality medical laboratory systems in resource-limited settings. Despite the low numbers of laboratories accredited to date, accreditation has the potential to improve the quality of health care for patients through the reduction of testing errors and attendant decreases in inappropriate treatment. Accredited laboratories can become more accountable and less dependent on external support. Efforts made to achieve accreditation may also lead to improvements in the management of laboratory networks by focusing attention on areas of greatest need and accelerating improvement in areas such as supply chain, training, and instrument maintenance. Laboratory accreditation may also have a positive influence on performance in other areas of health care systems by allowing laboratories to demonstrate high standards of service delivery. Accreditation may, thus, provide an effective mechanism for health system improvement yielding long-term benefits in the quality, cost-effectiveness, and sustainability of public health programs. Further studies are needed to strengthen the evidence on the benefits of accreditation and to justify the resources needed to implement accreditation programs aimed at improving the performance of laboratory systems.

Snap! Recognising implicit actions in static point-light displays.

Johansson (1973 Perception & Psychophysics 14 201-211) suggested that point-light displays that are static -- so-called 'snapshots' -- contain little or no information about the actor or their action. Here we present data that suggest even naive observers can perceive such information from static point-light arrays. Observers were able, at rates better than chance, to discriminate the directions of facing of sagittally viewed static point-light walkers. The data show also that, without feedback, performances improved with experience. Our data have implications for assumptions made in designing experiments with point-light displays and for models of the neural mechanisms mediating biological motion perceptions.

Identification of a distal GLUT4 trafficking event controlled by actin polymerization.

The insulin-stimulated trafficking of GLUT4 to the plasma membrane in muscle and fat tissue constitutes a central process in blood glucose homeostasis. The tethering, docking, and fusion of GLUT4 vesicles with the plasma membrane (PM) represent the most distal steps in this pathway and have been recently shown to be key targets of insulin action. However, it remains unclear how insulin influences these processes to promote the insertion of the glucose transporter into the PM. In this study we have identified a previously uncharacterized role for cortical actin in the distal trafficking of GLUT4. Using high-frequency total internal reflection fluorescence microscopy (TIRFM) imaging, we show that insulin increases actin polymerization near the PM and that disruption of this process inhibited GLUT4 exocytosis. Using TIRFM in combination with probes that could distinguish between vesicle transport and fusion, we found that defective actin remodeling was accompanied by normal insulin-regulated accumulation of GLUT4 vesicles close to the PM, but the final exocytotic fusion step was impaired. These data clearly resolve multiple steps of the final stages of GLUT4 trafficking, demonstrating a crucial role for actin in the final stage of this process.

Molecular dissection of the Munc18c/syntaxin4 interaction: implications for regulation of membrane trafficking.

Sec1p/Munc18 (SM) proteins are believed to play an integral role in vesicle transport through their interaction with SNAREs. Different SM proteins have been shown to interact with SNAREs via different mechanisms, leading to the conclusion that their function has diverged. To further explore this notion, in this study, we have examined the molecular interactions between Munc18c and its cognate SNAREs as these molecules are ubiquitously expressed in mammals and likely regulate a universal plasma membrane trafficking step. Thus, Munc18c binds to monomeric syntaxin4 and the N-terminal 29 amino acids of syntaxin4 are necessary for this interaction. We identified key residues in Munc18c and syntaxin4 that determine the N-terminal interaction and that are consistent with the N-terminal binding mode of yeast proteins Sly1p and Sed5p. In addition, Munc18c binds to the syntaxin4/SNAP23/VAMP2 SNARE complex. Pre-assembly of the syntaxin4/Munc18c dimer accelerates the formation of SNARE complex compared to assembly with syntaxin4 alone. These data suggest that Munc18c interacts with its cognate SNAREs in a manner that resembles the yeast proteins Sly1p and Sed5p rather than the mammalian neuronal proteins Munc18a and syntaxin1a. The Munc18c-SNARE interactions described here imply that Munc18c could play a positive regulatory role in SNARE assembly.