A protocol for a systematic review of clinical guidelines and published systematic reviews on the early detection of oral cancer

Background: The predicted increase in incidence of oral cavity cancer (OCC) coupled with high mortality and poor prognosis – particularly when diagnosed at a late/advanced stage – highlights the need for prevention and early detection/screening to reverse these trends. Dental healthcare professionals in primary care settings have a pivotal role in this effort. Aim: The aim of this protocol is to detail the process for assessing the evidence for the best practice and methods of early detection/screening for OCC in primary care dental settings by undertaking a systematic review of global clinical guidelines and published systematic reviews. Method: Searches for clinical guidelines and systematic reviews will be conducted in the following databases: Cochrane library, Medical Literature Analysis and Retrieval System Online (Ovid), Excerpta Medical dataBASE, PubMed, Turning Research into Practice, SCOPUS and Web of Science Core Collection. Our search will extend to include Google Scholar and international professional organizations/associations websites. In addition, we will handsearch the bibliographies and undertake citation searches of the selected papers. Quality appraisal will be undertaken using the Appraisal of Guidelines for Research and Evaluation version II instrument for the clinical guidelines and both A MeaSurement Tool to Assess Systematic Reviews and Risk of Bias in Systematic Reviews tools for the systematic reviews. A narrative synthesis approach will be used to assess the evidence of extracted data, primarily taking account of quality appraisal and recency of publication. Discussion: The synthesis of evidence will determine best practice for OCC early detection/screening by primary care dental healthcare professionals and will evaluate the relationship between clinical guidelines and the evidence base available from systematic reviews in this area

Distinct Types of Fibrocyte Can Differentiate from Mononuclear Cells in the Presence and Absence of Serum

Background: Ageing, immunity and stresstolerance are inherent characteristics of all organisms. In animals, these traits are regulated, at least in part, by forkhead transcription factors in response to upstream signals from the Insulin/Insulin–like growth factor signalling (IIS) pathway. In the nematode Caenorhabditis elegans, these phenotypes are molecularly linked such that activation of the forkhead transcription factor DAF-16 both extends lifespan and simultaneously increases immunity and stress resistance. It is known that lifespan varies significantly among the Caenorhabditis species but, although DAF-16 signalling is highly conserved, it is unclear whether this phenotypic linkage occurs in other species. Here we investigate this phenotypic covariance by comparing longevity, stress resistance and immunity in four Caenorhabditis species. Methodology/Principal Findings: We show using phenotypic analysis of DAF-16 influenced phenotypes that among four closely related Caenorhabditis nematodes, the gonochoristic species (Caenorhabditis remanei and Caenorhabditis brenneri) have diverged significantly with a longer lifespan, improved stress resistance and higher immunity than the hermaphroditic species (C. elegans and Caenorhabditis briggsae). Interestingly, we also observe significant differences in expression levels between the daf-16 homologues in these species using Real-Time PCR, which positively correlate with the observed phenotypes. Finally, we provide additional evidence in support of a role for DAF-16 in regulating phenotypic coupling by using a combination of wildtype isolates, constitutively active daf-16 mutants and bioinformatic analysis. Conclusions: The gonochoristic species display a significantly longer lifespan (p<0.0001) and more robust immune and stress response (p<0.0001, thermal stress; p<0.01, heavy metal stress; p<0.0001, pathogenic stress) than the hermaphroditic species. Our data suggests that divergence in DAF-16 mediated phenotypes may underlie many of the differences observed between these four species of Caenorhabditis nematodes. These findings are further supported by the correlative higher daf-16 expression levels among the gonochoristic species and significantly higher lifespan, immunity and stress tolerance in the constitutively active daf-16 hermaphroditic mutants

The development of a new generation of methyl chloride synthesis catalyst

In previous work by the authors, aspects of the surface chemistry connected with methyl chloride synthesis over an -alumina catalyst have been examined. This communication considers a role for Group 1 metal salts to modify the catalytic performance of the well characterised -alumina catalyst. Firstly, based on a previously postulated mechanism for the reaction of methanol on -alumina, a mechanism for methyl chloride synthesis over the -alumina catalyst is proposed. Secondly, the validity of the new mechanism is tested by observing how the (i) type and (ii) loading of the Group 1 metal salt may perturb methyl chloride selectivity. The outcomes of these measurements are rationalised with reference to the postulated mechanism. Overall, this study represents an example of how a proposed reaction mechanism has been used to inform and guide a catalyst development strategy for a large-scale industrial process

Investigating the acid site distribution of a new-generation methyl chloride synthesis catalyst

The effect of modifying an η-alumina methyl chloride synthesis catalyst by doping with CsCl and KCl over the concentration range of 0.1–1.0 mmol g(cat)–1 is investigated by a combination of pyridine chemisorption coupled with infrared spectroscopy and mass-selective temperature-programmed desorption measurements. The loading of group 1 metal chloride is equivalent to a titrant that enables selective neutralization of Lewis acid sites present at the surface of the reference η-alumina catalyst. Specifically, a loading of 0.1 mmol g(cat)–1 is sufficient to neutralize the strong Lewis acid sites; a loading of 0.6 mmol g(cat)–1 is sufficient to neutralize the strong and medium-strong Lewis acid sites; a loading of 1.0 mmol g(cat)–1 neutralizes all of the strong and medium-strong Lewis acid sites and partially neutralizes the medium-weak Lewis acid site. These deductions connect with a catalyst design program to develop a methyl chloride synthesis catalyst that exhibits minimal formation of the byproduct dimethyl ether

Disentangling the cause of a catastrophic population decline in a large marine mammal

Considerable uncertainties often surround the causes of long-term changes in population abundance. One striking example is the precipitous decline of southern sea lions (SSL; Otaria flavescens) at the Falkland Islands, from 80 555 pups in the mid 1930s to just 5506 pups in 1965. Despite an increase in SSL abundance over the past two decades, the population has not recovered, with the number of pups born in 2014 (minimum 4443 pups) less than 6% of the 1930s estimate. The order-of-magnitude decline is primarily attributed to commercial sealing in Argentina. Here, we test this established paradigm and alternative hypotheses by assessing (1) commercial sealing at the Falkland Islands, (2) winter migration of SSL from the Falkland Islands to Argentina, (3) whether the number of SSL in Argentina could have sustained the reported level of exploitation, and (4) environmental change. The most parsimonious hypothesis explaining the SSL population decline was environmental change. Specifically, analysis of 160 years of winter sea surface temperatures revealed marked changes, including a period of warming between 1930 and 1950 that was consistent with the period of SSL decline. Sea surface temperature changes likely influenced the distribution or availability of SSL prey and impacted its population dynamics. We suggest that historical harvesting may not always be the “smoking gun” as is often purported. Rather, our conclusions support the growing evidence for bottom-up forcing on the abundance of species at lower trophic levels (e.g., plankton and fish) and resulting impacts on higher trophic levels across a broad range of ecosystems

Spray drying as a reliable route to produce metastable carbamazepine form IV

Carbamazepine is an active pharmaceutical ingredient used in the treatment of epilepsy that can form at least five polymorphic forms. Metastable form IV was originally discovered from crystallisation with polymer additives however has not been observed from subsequent solvent only crystallisation efforts. This work reports the reproducible formation of phase pure crystalline form IV by spray drying of methanolic carbamazepine solution. Characterisation of the material was carried out using diffraction, SEM and DSC. In situ Raman spectroscopy was used to monitor the spray dried product during the spray drying process. This work demonstrates spray drying provides a robust method for the production of form IV carbamazepine and the combination of high supersaturation and rapid solid isolation from solution overcomes the apparent limitation of more traditional solution crystallisation approaches to produce metastable crystalline forms

Outcome measures for use in trials of paediatric otorrhoea:A systematic review

Introduction:Paediatric otorrhoea (PO) describes a middle ear infection that results in a perforation of the tympanic membrane and ear discharge, in children and young people (CYP). Prolonged infection may be associated with hearing loss and developmental delay. The current management of paediatric otorrhoea is variable, including non-invasive treatments (conservative, oral antibiotics, topical antibiotics) and surgery, reflecting the lack of a sufficiently strong evidence base. Outcome reporting is fundamental to producing reliable and meaningful evidence to inform best practice.Objectives:Primary objective: to determine which outcome measures are currently used to evaluate treatment success in studies of non-surgical treatments for paediatric otorrhoea. Secondary objectives: to identify outcome measurement instruments used in the literature and assess their applicability for use in clinical trials of PO.Methods:This systematic review was registered with PROSPERO (CRD42023407976). Database searches of EMBASE, MEDLINE and Cochrane was performed on June 6, 2023, covering from Jan 1995 to May 2023. Randomised controlled trials or study protocols involving CYP with PO were included following PRISMA guidelines. Risk of bias was assessed with Cochrane's tool.Results:Of the 377 papers identified, six were included in the systematic review. The primary outcome of five of the studies related to otorrhoea cessation; both time to cessation and proportion recovered at various time points were used as measures. Two measurement instruments were identified: Otitis Media-6 Questionnaire and the Institute for Medical Technology Assessment Productivity Cost Questionnaire. Both were shown to be applicable measurement instruments when used in clinical trials of PO.Conclusions:To promote homogeneity and facilitate meaningful comparison and combination of studies, we propose that time to cessation of otorrhoea from onset of otorrhoea should be used as the primary outcome in future studies. Further research is needed to establish if this is the most important outcome to children and their caregivers