General practitioner experience and perception of Child and Adolescent Mental Health Services (CAMHS) care pathways: a multimethod research study

This is the final version of the article. Available from BMJ Publishing via the DOI in this recordOBJECTIVES: This is a pilot study with the objective of investigating general practitioner (GP) perceptions and experiences in the referral of mentally ill and behaviourally disturbed children and adolescents. DESIGN: Quantitative analyses on patient databases were used to ascertain the source of referrals into Child and Adolescent Mental Health Services (CAMHS) and identify the relative contribution from GP practices. Qualitative semistructured interviews were then used to explore challenges faced by GPs in referring to CAMHS. SETTING: GPs were chosen from the five localities that deliver CAMHS within the local Trust (Peterborough City, Fenland, Huntingdon, Cambridge City and South Cambridgeshire). PARTICIPANTS: For the quantitative portion, data involving 19 466 separate referrals were used. Seven GPs took part in the qualitative interviews. RESULTS: The likelihood of a referral from GPs being rejected by CAMHS was over three times higher compared to all other referral sources combined within the Cambridge and Peterborough NHS Foundation Trust. Interviews showed that detecting the signs and symptoms of mental illness in young people is a challenge for GPs. Communication with referral agencies varies and depends on individual relationships. GPs determine whether to refer on a mixture of the presenting conditions and their perceived likelihood of acceptance by CAMHS; the criteria for the latter were poorly understood by the interviewed GPs. CONCLUSIONS: There are longstanding structural weaknesses in the services for children and young people in general, reflected in poor multiagency cooperation at the primary care level. GP-friendly guidelines and standards are required that will aid in decision-making and help with understanding the referrals process. We look to managers of both commissioning and providing organisations, as well as future research, to drive forward the development of tools, protocols, and health service structures to help aid the recognition and treatment of mental illness in young people.This work was supported by the National Institute for Health Research Collaborations for Leadership in Applied Health Research and Care (CLAHRC), grant number RNAG-186

Charge Generation and Selective Separation at PbS Quantum Dot Metal Oxide Interfaces

Charge separation and transfer at the interface between layers of oleic acid capped PbS quantum dots QDs and Titanium and Indium Tin oxide TiO2 and ITO films were investigated by surface photovoltage SPV measurements. Photoluminescence PL measurements were performed in order to check for excitonic transitions and determine the QD band gaps. The QDs diameter of 4.2 nm and 5.0 nm were estimated by using the PL band gaps and the theoretical equation derived by Wang et al. [J. Chem. Phys. 87 1987 7315]. The SPV spectra of the PbS QDs TiO2 system reveal a positive charge on the PbS film surface and show three distinguished regions which demonstrate i the charge separation across QDs, ii the electron injection from QDs into TiO2 and iii the fundamental absorption in TiO2. The on set of the electron injection depends on the QD size QD band gap it shifts to lower photon energies for lower QD dimensions for higher QD band gaps . Thus, a better conduction band alignment is achieved in the latter case. In contrast to PbS QDs TiO2, the SPV spectra of the PbS QDs ITO structure reveal the negative charge on PbS surface. Moreover, the charge transfer at this interface is not observed. Instead, the SPV peculiarities in the photon energy range 1.4 3.0 eV point out to trapped holes on the ITO surface state

Fluid flow stimulates chemoautotrophy in hydrothermally influenced coastal sediments

© The Author(s), 2022. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Sievert, S. M., Buehring, S., Gulmann, L. K., Hinrichs, K.-U., Ristova, P. P., & Gomez-Saez, G. Fluid flow stimulates chemoautotrophy in hydrothermally influenced coastal sediments. Communications Earth & Environment, 3(1), (2022): 96, https://doi.org/10.1038/s43247-022-00426-5.Hydrothermalism in coastal sediments strongly impacts biogeochemical processes and supports chemoautotrophy. Yet, the effect of fluid flow on microbial community composition and rates of chemoautotrophic production is unknown because rate measurements under natural conditions are difficult, impeding an assessment of the importance of these systems. Here, in situ incubations controlling fluid flow along a transect of three geochemically distinct locations at a shallow-water hydrothermal system off Milos (Greece) show that Campylobacteria dominated chemoautotrophy in the presence of fluid flow. Based on injected 13C-labelled dissolved inorganic carbon and its incorporation into fatty acids, we constrained carbon fixation to be as high as 12 µmol C cm−3 d−1, corresponding to areal rates up to 10-times higher than previously reported for coastal sediments, and showed the importance of fluid flow for supplying the necessary substrates to support chemoautotrophy. Without flow, rates were substantially lower and microbial community composition markedly shifted. Our results highlight the importance of fluid flow in shaping the composition and activity of microbial communities of shallow-water hydrothermal vents, identifying them as hotspots of microbial productivity.Open Access funding enabled and organized by Projekt DEAL

Starvation and recovery in the deep-sea methanotroph Methyloprofundus sedimenti

In the deep ocean, the conversion of methane into derived carbon and energy drives the establishment of diverse faunal communities. Yet specific biological mechanisms underlying the introduction of methane-derived carbon into the food web remain poorly described, due to a lack of cultured representative deep-sea methanotrophic prokaryotes. Here, the response of the deep-sea aerobic methanotroph Methyloprofundus sedimenti to methane starvation and recovery was characterized. By combining lipid analysis, RNA analysis, and electron cryotomography, it was shown that M. sedimenti undergoes discrete cellular shifts in response to methane starvation, including changes in headgroup-specific fatty acid saturation levels, and reductions in cytoplasmic storage granules. Methane starvation is associated with a significant increase in the abundance of gene transcripts pertinent to methane oxidation. Methane reintroduction to starved cells stimulates a rapid, transient extracellular accumulation of methanol, revealing a way in which methane-derived carbon may be routed to community members. This study provides new understanding of methanotrophic responses to methane starvation and recovery, and lays the initial groundwork to develop Methyloprofundus as a model chemosynthesizing bacterium from the deep sea

Studying feasibility and effects of a two-stage nursing staff training in residential geriatric care using a 30 month mixed-methods design [ISRCTN24344776]

<p>Abstract</p> <p>Background</p> <p>Transfer techniques and lifting weights often cause back pain and disorders for nurses in geriatric care. The Kinaesthetics care conception claims to be an alternative, yielding benefits for nurses as well as for clients.</p> <p>Starting a multi-step research program on the effects of Kinaesthetics, we assess the feasibility of a two-stage nursing staff training and a pre-post research design. Using quantitative and qualitative success criteria, we address mobilisation from the bed to a chair and backwards, walking with aid and positioning in bed on the staff level as well as on the resident level. In addition, effect estimates should help to decide on and to prepare a controlled trial.</p> <p>Methods/Design</p> <p>Standard basic and advanced Kinaesthetics courses (each comprising four subsequent days and an additional counselling day during the following four months) are offered to n = 36 out of 60 nurses in a residential geriatric care home, who are in charge of 76 residents. N = 22 residents needing movement support are participating to this study.</p> <p>On the staff level, measurements include focus group discussions, questionnaires, physical strain self-assessment (Borg scale), video recordings and external observation of patient assistance skills using a specialised instrument (SOPMAS). Questionnaires used on the resident level include safety, comfort, pain, and level of own participation during mobilisation. A functional mobility profile is assessed using a specialised test procedure (MOTPA).</p> <p>Measurements will take place at baseline (T0), after basic training (T1), and after the advanced course (T2). Follow-up focus groups will be offered at T1 and 10 months later (T3).</p> <p>Discussion</p> <p>Ten criteria for feasibility success are established before the trial, assigned to resources (missing data), processes (drop-out of nurses and residents) and science (minimum effects) criteria. This will help to make rational decision on entering the next stage of the research program.</p> <p>Trial Registration</p> <p>Current Controlled Trials <a href="http://www.controlled-trials.com/ISRCTN24344776">ISRCTN24344776</a>.</p

Hydrazones and Thiosemicarbazones Targeting Protein-Protein-Interactions of SARS-CoV-2 Papain-like Protease

The papain-like protease (PLpro) of SARS-CoV-2 is essential for viral propagation and, additionally, dysregulation of the host innate immune system. Using a library of 40 potential metal-chelating compounds we performed an X-ray crystallographic screening against PLpro. As outcome we identified six compounds binding to the target protein. Here we describe the interaction of one hydrazone (H1) and five thiosemicarbazone (T1-T5) compounds with the two distinct natural substrate binding sites of PLpro for ubiquitin and ISG15. H1 binds to a polar groove at the S1 binding site by forming several hydrogen bonds with PLpro. T1-T5 bind into a deep pocket close to the polyubiquitin and ISG15 binding site S2. Their interactions are mainly mediated by multiple hydrogen bonds and further hydrophobic interactions. In particular compound H1 interferes with natural substrate binding by sterical hindrance and induces conformational changes in protein residues involved in substrate binding, while compounds T1-T5 could have a more indirect effect. Fluorescence based enzyme activity assay and complementary thermal stability analysis reveal only weak inhibition properties in the high micromolar range thereby indicating the need for compound optimization. Nevertheless, the unique binding properties involving strong hydrogen bonding and the various options for structural optimization make the compounds ideal lead structures. In combination with the inexpensive and undemanding synthesis, the reported hydrazone and thiosemicarbazones represent an attractive scaffold for further structure-based development of novel PLpro inhibitors by interrupting protein-protein interactions at the S1 and S2 site

Microtubules gate tau condensation to spatially regulate microtubule functions.

Tau is an abundant microtubule-associated protein in neurons. Tau aggregation into insoluble fibrils is a hallmark of Alzheimer's disease and other types of dementia1, yet the physiological state of tau molecules within cells remains unclear. Using single-molecule imaging, we directly observe that the microtubule lattice regulates reversible tau self-association, leading to localized, dynamic condensation of tau molecules on the microtubule surface. Tau condensates form selectively permissible barriers, spatially regulating the activity of microtubule-severing enzymes and the movement of molecular motors through their boundaries. We propose that reversible self-association of tau molecules, gated by the microtubule lattice, is an important mechanism of the biological functions of tau, and that oligomerization of tau is a common property shared between the physiological and disease-associated forms of the molecule

Platelet‐Derived Growth Factor Promotes Periodontal Regeneration in Localized Osseous Defects: 36‐Month Extension Results From a Randomized, Controlled, Double‐Masked Clinical Trial

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141092/1/jper0456.pd