A biologically relevant rapid quantification of physical and biological stress profiles on rocky shores.

Different combinations and intensities of physical (e.g. thermal) and biological (e.g.competition or predation) stress operate on organisms in different locations. Variation in these stresses can occur over small to medium spatial scales (cm to 10s m) in heterogeneous environments such as rocky shores, due to differences in sun and wave exposure, shore topography and/or recruitment. In this study we demonstrate how simple measurements can be taken that represent physical and biological stresses (stress profiles)in a given location. Using a bootstrapped principal component analysis, we identified significantly different stress profiles at four sites separated by only 10s to 100s of metres on the Shek O peninsula in Hong Kong. We then measured response to thermal stress, as determined by detachment temperature, in the limpet Cellana grata (which is known to be a sensitive indicator species to thermal stress) from each location. Significant differences in stress profile between locations were also seen in thermal stress tolerance of limpets from those locations. At locations where the major stresses are likely to be more physical or less biological in nature (e.g. southerly facing aspect or lower density of grazers), the mean detachment temperature was higher, whereas detachment temperature was lower at sites with more biological or less physical stress. This method is, therefore, able to determine biologically meaningful differences in stress profiles over small to medium spatial scales, and demonstrates that localised adaptation (i.e. post planktonic settlement) or acclimation of species may occur in response to these different stress profiles. The technique can be adapted to different environments and smaller or larger spatial scales as long as the stress experienced by the study species is relevant to these scales

Neutron total cross sections on nuclei at Fermilab energies

We have measured total cross sections for neutrons on protons, deuteriom, beryllium, carbon, aluminium, iron, copper, cadmium, tungsten, lead, and uranium for momenta between 30 and 300 GeV/c. The measurements were carried out in a small-angle neutral beam at Fermilab. Typical accuracy of the data is 0.5 to 1%. The cross sections are consistent with an A0.77+/-0.01 dependence over the entire momentum range. The cross sections are compared with theoretical predictions. Agreement is found only if inelastic screening is included. Nuclear radii obtained from our data are in good agreement with previous determinations.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/22036/1/0000454.pd

Design, Synthesis, and Evaluation of Lung-Retentive Prodrugs for Extending the Lung Tissue Retention of Inhaled Drugs

A major limitation of pulmonary delivery is that drugs can exhibit suboptimal pharmacokinetic profiles resulting from rapid elimination from the pulmonary tissue. This can lead to systemic side effects and a short duration of action. A series of dibasic dipeptides attached to the poorly lung-retentive muscarinic M3 receptor antagonist piperidin-4-yl 2-hydroxy-2,2-diphenylacetate (1) through a pH-sensitive-linking group have been evaluated. Extensive optimization resulted in 1-(((R)-2-((S)-2,6-diaminohexanamido)-3,3-dimethylbutanoyl)oxy)ethyl 4-(2-hydroxy-2,2-diphenylacetoxy)piperidine-1-carboxylate (23), which combined very good in vitro stability and very high rat lung binding. Compound 23 progressed to pharmacokinetic studies in rats, where, at 24 h post dosing in the rat lung, the total lung concentration of 23 was 31.2 μM. In addition, high levels of liberated drug 1 were still detected locally, demonstrating the benefit of this novel prodrug approach for increasing the apparent pharmacokinetic half-life of drugs in the lungs following pulmonary dosing

unDerstandIng the cauSes of mediCation errOrs and adVerse drug evEnts for patients with mental illness in community caRe (DISCOVER): a qualitative study

BackgroundIt is estimated that 237 million medication errors occur in England each year with a significant number occurring in the community. Our understanding of the causes of preventable medication errors and adverse drug events (ADE) affecting patients with mental illness is limited in this setting. Better understanding of the factors that contribute to errors can support the development of theory-driven improvement interventions.MethodsRemote qualitative semi-structured interviews with 26 community-based healthcare professionals in England and Wales were undertaken between June–November 2022. Recruitment was undertaken using purposive sampling via professional networks. Interviews were guided by the critical incident technique and analysed using the framework method. Any data that involved speculation was not included in the analysis. Independent analysis was carried out by the research team to extract themes guided by the London Protocol.ResultsA total of 43 medication errors and 12 preventable ADEs were discussed, with two ADEs having an unknown error origin. Prescribing errors were discussed most commonly (n = 24), followed by monitoring errors (n = 8). Six contributory factor themes were identified: the individual (staff); the work environment; the teams/interfaces; the organisation and management; the patient; and the task and technology. The individual (staff) factors were involved in just over 80% of all errors discussed. Participants reported a lack of knowledge regarding psychotropic medication and mental illnesses which accompanied diffusion of responsibility. There were difficulties with team communication, particularly across care interfaces, such as ambiguity/brevity of information being communicated and uncertainty concerning roles which created confusion amongst staff. Unique patient social/behavioural contributory factors were identified such as presenting with challenging behaviour and complex lifestyles, which caused difficulties attending appointments as well as affecting overall clinical management.ConclusionThese findings highlight that the causes of errors are multifactorial with some unique to this patient group. Key areas to target for improvement include the education/training of healthcare professionals regarding neuropharmacology/mental illnesses and enhancing communication across care interfaces. Future research should explore patient perspectives regarding this topic to help develop a holistic picture. These findings can be used to guide future intervention research to ameliorate medication safety challenges for this patient group

Neutron-proton differential cross sections in the range 70 to 400 GeV/c

We report the results of an experiment which measured np elastic scattering differential cross sections over a range in -t from 0.15 to ~3.6 (GeV/c)2 for incident neutron momenta from 70 to 400 GeV/c. We find the logarithmic slope parameter, evaluated at -t = 0.2 (GeV/c)2, to be consistent with existing proton-proton parametrizations. The data exhibit a dip in the cross section near -t = 1.4 (GeV/c)2 for incident neutron momenta above 200 GeV/c. For neutron momenta less than 280 GeV/c, the neutron-proton cross sections are found to be higher than existing proton-proton data in the range 0.7 [les] -t [les] 1.3 (GeV/c)2 which is in contradiction to most Regge predictions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/23627/1/0000590.pd

The Athena x-ray optics development and accommodation

The Athena mission, under study and preparation by ESA as its second Large-class science mission, requires the largest X-ray optics ever flown, building on a novel optics technology based on mono crystalline silicon. Referred to as Silicon Pore Optics technology (SPO), the optics is highly modular and benefits from technology spin-in from the semiconductor industry. The telescope aperture of about 2.5 meters is populated by around 700 mirror modules, accurately co-aligned to produce a common focus. The development of the SPO technology is a joint effort by European industrial and research entities, working together to address the challenges to demonstrate the imaging performance, robustness and efficient series production of the Athena optics. A technology development plan was established and is being regularly updated to reflect the latest developments, and is fully funded by the ESA technology development programmes. An industrial consortium was formed to ensure coherence of the individual technology development activities. The SPO technology uses precision machined mirror plates produced using the latest generation top quality 12 inch silicon wafers, which are assembled into rugged stacks. The surfaces of the mirror plates and the integral support structure is such, that no glue is required to join the individual mirror plates. Once accurately aligned with respect to each other, the surfaces of the mirror plates merge in a physical bonding process. The resultant SPO mirror modules are therefore very accurate and stable and can sustain the harsh conditions encountered during launch and are able to tolerate the space environment expected during operations. The accommodation of the Athena telescope is also innovative, relying on a hexapod mechanism to align the optics to the selected detector instruments located in the focal plane. System studies are complemented by dedicated technology development activities to demonstrate the capabilities before the adoption of the Athena mission

Long Distance Dispersal and Connectivity in Amphi-Atlantic Corals at Regional and Basin Scales

Among Atlantic scleractinian corals, species diversity is highest in the Caribbean, but low diversity and high endemism are observed in various peripheral populations in central and eastern Atlantic islands and along the coasts of Brazil and West Africa. The degree of connectivity between these distantly separated populations is of interest because it provides insight into processes at both evolutionary and ecological time scales, such as speciation, recruitment dynamics and the persistence of coral populations. To assess connectivity in broadly distributed coral species of the Atlantic, DNA sequence data from two nuclear markers were obtained for six coral species spanning their distributional ranges. At basin-wide scales, significant differentiation was generally observed among populations in the Caribbean, Brazil and West Africa. Concordance of patterns in connectivity among co-distributed taxa indicates that extrinsic barriers, such as the Amazon freshwater plume or long stretches of open ocean, restrict dispersal of coral larvae from region to region. Within regions, dispersal ability appears to be influenced by aspects of reproduction and life history. Two broadcasting species, Siderastrea siderea and Montastraea cavernosa, were able to maintain gene flow among populations separated by as much as 1,200 km along the coast of Brazil. In contrast, brooding species, such as Favia gravida and Siderastrea radians, had more restricted gene flow along the Brazilian coast

Reviews and bibliographical notices

n/

Minimal information for studies of extracellular vesicles 2018 (MISEV2018):a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points