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Additional file 1: Figure S1. ML species and consensus phylogenies for each genus. Figure S2. rRNA HGT ML phylogenies for each genus. Figure S3. rRNA gene copy numbers for each species. Figure S4. 16S rRNA gene hypervariable region concordance for each genus. Figure S5. Gene length versus concordance for each genus. Figure S6. SNP count versus concordance for each SNP category and genus. Figure S7. Average level of concordance and SNP count for genes associated with universal GO terms. Figure S8. ML inter-genus phylogeny (includes individual species names). Figure S9. SNP proportion versus concordance for each SNP category.

Additional file 1.

Additional file 1. COVID-19 SAVER policy.

Additional file 3. Patient consent form.

Additional file 2. Patient information sheet.

Additional file 1. SPIRIT 2013 Checklist: Recommended items to address in a clinical trial protocol and related documents*.

This paper draws on the poetic concept of the oneness of the self and the world, as elaborated through Coleridge's reading of German romantic philosophers by the poet William Wordsworth. In his poem "Prelude" he rejects simple materialism and simple spiritualism, just as Schelling rejected the extreme views that the spiritual self creates the world or that the material world is created by the self. Wordsworth claims that things are half created and half perceived, and that there are ennobling interchanges between the world and the self. The notion of oneness, of the merging of inner and outer, perceived and the perceiver, has been influential on numerous and diverse poets. In the paper, I compare various modes of vision that attempt to reveal this oneness in Slovenian poets such as Prešeren, Kosovel, Detela and Osojnik on the one hand, and Wright, Oliver, Murray, Stevens and Strand among American writers. The question of influence is at least ambiguous, but what I am suggesting is some likenesses that seem to emerge from the act searching the world through writing. Prispevek izhaja iz poetičnega koncepta enosti jaza in sveta, kot ga je skozi Coleridgeevo branje nemških romantičnih filozofov izoblikoval pesnik William Wordsworth. Ta v svoji pesnitvi "Preludij" zavrača preprosti materializem in preprosti spiritualizem, podobno kot je Schelling zavrnil skrajni stališči, da poduhovljeni jaz ustvari svet ali da materialni svet ustvari jaz. Wordsworth trdi, da so stvari pol ustvarjene in pol zaznane, med svetom in jazom pa prihaja do oplajajočih izmenjav. Ideja o enosti, o zlivanju notranjosti in zunanjosti, zaznanega in zaznavajočega, je vplivala na številne in različne pesnike. V članku primerjam različne načine videnja, ki skušajo razkriti omenjeno enost, in sicer pri slovenskih pesnikih, kot so Prešeren, Kosovel, Detela in Osojnik na eni strani, ter pri Jamesu Wrightu, Mary Oliver, Joan Murray, Wallacu Stevensu in Marku Strandu med ameriškimi pisatelji. Vprašanje vpliva je vsaj dvoumno, toda kar nakazujem, je določena podobnost, za katero se zdi, da izhaja iz dejanja, ki svet raziskuje skozi pisanje.

Supplemental material, Appendix for Practical perspective of cricket ball swing by James A Scobie, William P Shelley, Richard W Jackson, Simon P Hughes and Gary D Lock in Proceedings of the Institution of Mechanical Engineers, Part P: Journal of Sports Engineering and Technology

Background: Diabetes mellitus is frequently observed in pancreatic cancer patients and is both a risk factor and an early manifestation of the disease. Methods: We analysed the prognostic impact of diabetes on the outcome of pancreatic cancer following resection and adjuvant chemotherapy using individual patient data from three European Study Group for Pancreatic Cancer randomised controlled trials. Analyses were carried out to assess the association between clinical characteristics and the presence of preoperative diabetes, as well as the effect of diabetic status on overall survival. Results: In total, 1105 patients were included in the analysis, of whom 257 (23%) had confirmed diabetes and 848 (77%) did not. Median (95% confidence interval (CI)) unadjusted overall survival in non-diabetic patients was 22.3 (20.8–24.1) months compared with 18.8 (16.9–22.1) months for diabetic patients (P=0.24). Diabetic patients were older, had increased weight and more co-morbidities. Following adjustment, multivariable analysis demonstrated that diabetic patients had an increased risk of death (hazard ratio: 1.19 (95% CI 1.01, 1.40), P=0.034). Maximum tumour size of diabetic patients was larger at randomisation (33.6 vs 29.7 mm, P=0.026). Conclusions: Diabetes mellitus was associated with increased tumour size and reduced survival following pancreatic cancer resection and adjuvant chemotherapy.

Randomised Clinical Trials (RCT) are one of the most powerful tools of medical re- search and provide the basis for changing clinical practice. In oncology, the RCT is of particular importance in searching for new therapies and treatment approaches for patients diagnosed with cancer. Many of these trials have overall survival as a primary endpoint and are often designed with marginal e�ects being of clinical interest. As a result trials are typically large and are expensive in both time and money. Given the substantial cost involved in running clinical trials, it is an ethical imper- ative that statisticians endeavour to make the most e�cient use of any data obtained. A number of methods are explored in this thesis for the analysis of survival data from clinical trials with this e�ciency in mind. Statistical methods of analysis which take account of extreme values of covariates are proposed as well as a method for the analysis of survival data where the assumption of proportionality cannot be assumed. Beyond this, Bayesian theory applied to oncology studies is explored with examples of Bayesian survival models used in a study of pancreatic cancer. Also using a Bayesian approach, methodology for the design and analysis of trial data is proposed whereby trial data are supplemented by the information taken from previous trials. Arguments are made towards unequal allocation ratios for future trials with informative prior distributions.

Focus group questions. Additional file 1 shows leading focus group questions in the three categories of caries etiology, prevention and barriers to oral care. (DOCX 76 kb)

This is the Molecule of the Month entry for June 1997 about triphenylmethyl. It is a pdf archive version of the HTML webpage.

OBJECTIVE: To investigate whether cannabis use is associated with increased risk of relapse, as indexed by number of hospital admissions, and whether antipsychotic treatment failure, as indexed by number of unique antipsychotics prescribed, may mediate this effect in a large data set of patients with first episode psychosis (FEP).DESIGN: Observational study with exploratory mediation analysis.SETTING: Anonymised electronic mental health record data from the South London and Maudsley NHS Foundation Trust.PARTICIPANTS: 2026 people presenting to early intervention services with FEP.EXPOSURE: Cannabis use at presentation, identified using natural language processing.MAIN OUTCOME MEASURES: admission to psychiatric hospital and clozapine prescription up to 5 years following presentation.MEDIATOR: Number of unique antipsychotics prescribed.RESULTS: Cannabis use was present in 46.3% of the sample at first presentation and was particularly common in patients who were 16-25, male and single. It was associated with increased frequency of hospital admission (incidence rate ratio 1.50, 95% CI 1.25 to 1.80), increased likelihood of compulsory admission (OR 1.55, 1.16 to 2.08) and greater number of days spent in hospital (β coefficient 35.1 days, 12.1 to 58.1). The number of unique antipsychotics prescribed, mediated increased frequency of hospital admission (natural indirect effect 1.09, 95% CI 1.01 to 1.18; total effect 1.50, 1.21 to 1.87), increased likelihood of compulsory admission (natural indirect effect (NIE) 1.27, 1.03 to 1.58; total effect (TE) 1.76, 0.81 to 3.84) and greater number of days spent in hospital (NIE 17.9, 2.4 to 33.4; TE 34.8, 11.6 to 58.1).CONCLUSIONS: Cannabis use in patients with FEP was associated with an increased likelihood of hospital admission. This was linked to the prescription of several different antipsychotic drugs, indicating clinical judgement of antipsychotic treatment failure. Together, this suggests that cannabis use might be associated with worse clinical outcomes in psychosis by contributing towards failure of antipsychotic treatment.

Quantitative survey. Structured survey questions are provided in Additional file 2. (PDF 500 KB)

Qualitative interview process. Full description of the qualitative interview process, including the semi-structured interview guide, is provided in Additional file 1. (PDF 337 KB)

Background: Bipolar disorder is a significant cause of morbidity and mortality. Although existing treatments are effective, there is often a substantial delay before diagnosis and treatment initiation. We sought to investigate factors associated with the delay before diagnosis of bipolar disorder and the onset of treatment in secondary mental healthcare. Method: Retrospective cohort study using anonymised electronic mental health record data from the South London and Maudsley NHS Foundation Trust (SLaM) Biomedical Research Centre (BRC) Case Register on 1364 adults diagnosed with bipolar disorder between 2007 and 2012. The following predictor variables were analysed in a multivariable Cox regression analysis: age, gender, ethnicity, compulsory admission to hospital under the UK Mental Health Act, marital status and other diagnoses prior to bipolar disorder. The outcomes were time to recorded diagnosis from first presentation to specialist mental health services (the diagnostic delay), and time to the start of appropriate therapy (treatment delay). Results: The median diagnostic delay was 62 days (interquartile range: 17-243) and median treatment delay was 31 days (4-122). Compulsory hospital admission was associated with a significant reduction in both diagnostic delay (hazard ratio 2.58, 95% CI 2.18-3.06) and treatment delay (4.40, 3.63-5.62). Prior diagnoses of other psychiatric disorders were associated with increased diagnostic delay, particularly alcohol (0.48, 0.33-0.41) and substance misuse disorders (0.44, 0.31- 0.61). Prior diagnosis of schizophrenia and psychotic depression were associated with reduced treatment delay. Conclusions: Some individuals experience a significant delay in diagnosis and treatment of bipolar disorder after initiation of specialist mental healthcare, particularly those who have prior diagnoses of alcohol and substance misuse disorders. These findings highlight a need for further study on strategies to better identify underlying symptoms and offer appropriate treatment sooner in order to facilitate improved clinical outcomes, such as developing specialist early intervention services to identify and treat people with bipolar disorder.

The difference in stellar structure above and below spectral type ~M4 is expected to be a very important one, connected directly or indirectly to a variety of observational phenomena in cool stars---such as rotation, activity, magnetic field generation and topology, timescales for evolution of these, and even the basic mass-radius relationship. In this Cool Stars XVI Splinter Session, we aimed to use the M4 transition as an opportunity for discussion about the interiors of low-mass stars and the mechanisms which determine their fundamental properties. By the conclusion of the session, several key points were elucidated. Although M dwarfs exhibit significant changes across the fully convective boundary, this "M4 transition" is not observationally sharp or discrete. Instead, the properties of M dwarfs (i.e. radius, effective temperature, rotation, activity lifetime, magnetic field strength and topology) show smooth changes across M3--M6 spectral types. In addition, a wide range of stellar masses share similar spectral types around the fully convective transition. There appears to be a second transition at M6--M8 spectral types, below which there exists a clear dichotomy of magnetic field topologies. Finally, we used the information and ideas presented in the session to construct a framework for how the structure of an M dwarf star, born with specific mass and chemical composition, responds to the presence of its magnetic field, itself driven by a feedback process that links the star's rotation, interior structure, and field topology., Comment: Report from Cool Stars XVI Splinter Session, to appear in CS16 Proceedings. 12 pages, 10 figures. Fixed typos and problems with some figures

The effect of apolipoproteins on the hepatic lipase-catalyzed hydrolysis of high density lipoprotein (HDL) triacylglycerols was studied in an in vitro system consisting of purified human post-heparin hepatic lipase, HDL2 and albumin. The apparent values of the Michaelis constant (Km) and maximal velocity (Vmax) for the hepatic lipase-catalyzed hydrolysis of HDL2-triacylglycerols were 0.18 mM and 86 nmol free fatty acids released/mg hepatic lipase per min, respectively. The addition of purified human plasma apolipoprotein A-I, A-II, E, C-I or C-III2 (containing 2 mol of sialic acid) to HDL2 caused inhibition of hepatic lipase activity. At a 1:1 weight ratio of added apolipoprotein to HDL2-protein, inhibition was 50% for apolipoprotein E and over 75% for the other apolipoproteins tested. Inhibition of enzyme activity occurred with both the unfractionated HDL2 and the HDL which were reisolated by ultracentrifugation. The major alteration in the composition of the reisolated HDL was an increase in the protein to phospholipid ratio. Based on these results, we speculate on the possible role of the apolipoproteins in the metabolism of HDL2 by hepatic lipase.

Significant process improvements developed in recent years have resulted in the production of a better quality of insulin suitable for formulation as soluble insulin at a neutral pH. The neutral regular insulin (NRI) selected for study and clinical trial was an unbuffered preparation obtained by simple neutralization of an acid regular insulin solution (ARI) to pH 7.4. Buffering appeared unnecessary and either phenol or methylparaben may be used as a preservative. Beef and pork insulins were readily soluble at neutral pH which suggested that purity is the prerequisite for solubility. NRI was compared with commercial ARI prepared from the same zinc-insulin crystals. NRI was shown to be more stable when stored at room temperature or above. Degradation reactions in NRI were similar to those in ARI but occurred at a slower rate. Mixtures of NRI or ARI with prolonged acting insulins showed comparable biological activity even though ARI affects the pH of the mixture. The results of this investigation have shown NRI to possess sufficient advantage over ARI to warrant consideration as a pharmaceutical form of soluble regular insulin and as a replacement for the conventional acidic form.

Background Complications after major surgery are a significant cause of morbidity and mortality. Neck Dissection (ND) is one of the most commonly performed major operations in Head and Neck Surgery (HNS). Significant surgical complications occur in approximately 10 ��� 40% of all patients. A systematic review and meta-analysis of randomised controlled trials (RCT) suggests that Fibrin Sealants (FS) may have potential clinical advantages in HNS through the reduction of complications, volume of wound drainage and retention time of the drains. So far, all RCTs have been single centre explanatory studies that lack external validity and are of variable quality. The paucity of high-quality pragmatic trials means that a surgical trial to determine the effectiveness of FS in reducing the rate and severity of complications in patients undergoing lateral neck dissection is warranted. The DEFeND randomised external pilot trial (REPT) will address critical questions on how well key components of the proposed study design work together as well as the feasibility of a definitive trial. Currently a Core Outcome Set (COS) for HNS does not exist and there is a paucity of patient centred outcome measures specific to HNS. A scoping review of surgical COS is proposed to guide the direction of future HNS outcomes research. Methods The trial design that is being piloted is that of a two arm, parallel group, superiority trial with block randomisation in a 1:1 allocation ratio. The interventional arm will constitute the application of FS (ARTISS, Baxter Healthcare Ltd) to the surgical wound following completion of ND in addition to standard of care (SoC). The control arm will constitute SoC alone. Patients will be recruited from two sites, Aintree University Hospital (AUH) and Queen Victoria Hospital (QVH). Eligible patients will include patients who require a lateral neck dissection with a minimum of three cervical nodal levels. Patients who require bilateral neck procedures or undergoing immediate reconstruction with free or regional flaps will be excluded. The outcomes being assessed are recruitment rate; screened to randomisation rate; fidelity of blinding process using blinding indices; number of missing or incomplete data entries; number of protocol deviations; number of losses to follow-up. A scoping review of surgical COS registered with the COMET database will be undertaken. Only COS in which patients or their carers are stakeholders will be included. The suitability of outcome measures proposed for the definitive DEFeND trial will also be discussed. Results Overall, the trial recruited ahead of time and target. Out of 101 eligible patients 48 (47.5%) were randomised successfully at a rate of 5.3 patients per month. Five patients were withdrawn from the trial before surgery due to a change in treatment plan that meant they were no longer eligible. Blinding of patients, Research Nurses and outcome assessors was effective as determined by blinding indices. Missing outcome data was low and there were no differences between treatment arm and site. Two significant protocol deviations were reported relating to the allocation reveal at a specific time point during surgery. Both occurred early in the trial and were not repeated after corrective and preventative actions. Two (4%) patients were lost to follow-up. The scoping review yielded 207 outcomes from 19 surgically relevant COS published between 2014 ��� 2020. Outcomes were classified (humanistic (71), complications (57), measurements (39), resource use (22), mortality (18)). Humanistic and complication outcomes were the most frequently utilised in surgical COS. Conclusion The DEFeND REPT has demonstrated that many components of the trial design work well together and a definitive pragmatic trial is feasible. Refinements in trial design and conduct are discussed and have the potential to improve the performance of the trial even further. The process has also revealed an important deficiency in patient centred outcomes that needs to be addressed before a definitive trial can be commenced. The validity and reliability of the Clavien-Dindo classification of surgical complications is discussed. Developing a COS for HNS trials is an important first step in identifying and developing patient centred outcomes. Consideration should be given to using patient reported outcome measures (PROM) for subjective core outcomes. This study has shown that PROMs are both acceptable and feasible in HNS trials.