Is sonographic intra-nodular vascularity a reliable predictor of thyroid malignancy? A UK tertiary centre study.

OBJECTIVE: British Thyroid Association 2014 guidelines emphasised ultrasound assessment of nodules. One ultrasonographic differentiator of debatable relevance is intra-nodular vascularity. This is the first UK study conducted to address this question. METHODS: Ultrasound reports for thyroid surgery patients over 10 years were retrospectively reviewed. Reports documenting 'intra-nodular vascularity or flow' were analysed. Reports identifying peripheral vascularity only or no intra-nodular flow formed the control group. Concordance with final histology was used to determine the odds ratio for malignancy. RESULTS: A total of 306 patients were included, and 119 (38.9 per cent) nodules demonstrated intra-nodular vascularity. Of these, 60 (50.4 per cent) were malignant compared with 42 per cent in the control group. Intra-nodular vascularity was not a statistically significant predictor of malignancy with an odds ratio of 1.39 (p = 0.18, 95 per cent confidence interval, 0.86-2.23). CONCLUSION: Intra-nodular vascularity in isolation was not a reliable predictor of malignancy. This supports other world literature studies. Although intra-nodular flow should not be relied upon in isolation, interpretation in conjunction with other suspicious findings enhances the predictive value.

Triage Into the Community for COVID-19 (TICC-19) Patients Pathway - Service evaluation of the virtual monitoring of patients with COVID pneumonia.

INTRODUCTION: COVID-19 pneumonia presented a unique problem for healthcare systems with the potential to overwhelm hospitals and lead to unnecessary morbidity and mortality. Safe triage and follow up systems are required to manage this unprecedented demand. METHODS: We designed a pathway for the triage and assessment of patients based on their resting oxygen saturations and response to a 30 metre rapid walking test. We admitted patients to a 'Virtual Ward' for remote oximetry monitoring from the Emergency Department, step down from inpatient wards and from the local Primary Care 'Hot Hub'. This allowed the safe and managed readmission of those patients who deteriorated at home. RESULTS: During the first wave of COVID-19 we entered 273 onto the pathway for Virtual Ward follow up. Of these, 31 patients were readmitted to hospital, two were admitted to Intensive Care and one patient died. Median oxygen saturation at presentation was 97 % (IQR 96-98%) and following a 30 metre walk test 96% (IQR 94-97%). Median NEWS-2 score was 2 (IQR 1-3). On feedback 99.5% of patients were likely or extremely likely to recommend the service to their family and friends. There was a cost avoidance of £107,600 per month. CONCLUSION: It is safe, feasible and cost effective to set up a triage system with remote oximetry monitoring for patients with COVID-19 and overwhelmingly patients find it a positive experience.

Abnormal Lung Point-of-Care Ultrasound (POCUS) in Suspected Cases of COVID-19 pneumonia with Normal Plain Chest Radiographs - A Case Series.

COVID-19 pneumonia produces a heterogeneous array of clinical, biochemical, and radiological findings. Over the last few months of global hurry to optimize a testing strategy, it has been suggested that bedside point-of-care lung ultrasound may have a diagnostic role. We present 3 patients with RT-PCR nasopharyngeal swab-confirmed COVID-19 pneumonia, who had an admission plain chest film reported to be normal by a consultant radiologist, but with significant sonographic abnormalities on bedside ultrasound performed within 24 hours of the chest radiograph. Lung ultrasound may better correlate with the oxygen requirement and overall condition of the patient than chest radiographs - a pertinent consideration given the imminent advance of the pandemic into resource-poor zones where timely access to roentgenological imaging may be sparse.

Editorial: POCUS in Acute Medicine.

In this edition of Acute Medicine, Knight et al. demonstrate from SAMBA data that access to ultrasound machines and supervision is geographically heterogeneous. They raise concerns that this may lead to inequity of provision of Point of Care Ultrasound(POCUS) and the benefits it can provide for patients. This point is well made: Since the development of the Focused Acute Medicine Ultrasound (FAMUS) competencies in 2016 there has been a steady increase in the provision of supervisors to 80 and the number of individuals completing training has increased to 56. Whilst this is to be applauded, our experience concurs with this paper that much of the ultrasound training is concentrated in pockets of expertise in particular hospitals.

Focused Acute Medicine Ultrasound (FAMUS).

Point of care ultrasound (POCUS) has seen steady growth in its use and applications in aiding clinicians in the management of acutely unwell patients. Focused Acute Medicine Ultrasound (FAMUS) is the standard created specifically for Acute Medicine physicians and is endorsed by the Society for Acute Medicine and recognised by the Acute Internal Medicine (AIM) training committee as a specialist skill. In this document we present a curriculum mapping exercise which utilises a 'knowledge, skills and behaviours' framework and incorporates the GMC's 'Good Medical Practice' (GMP) domains. We believe this will provide a standard for consideration of integrating focused ultrasound in AIM training programmes, with the aim of ultimately incorporating FAMUS as a core skill for all AIM trainees.

Curriculum mapping for Focused Acute Medicine Ultrasound (FAMUS).

Point of care ultrasound (POCUS) in the hands of the non-radiologist has seen a steady growth in popularity amongst emergency, intensive care and acute medical physicians. Increased accessibility to portable, purpose-built ultrasound machines has meant that clinicians often have access to a safe and non-invasive tool to enhance their management of the unwell.

Electrochemical and chemical routes to hydride loss from an iridium dihydride.

With a view towards replacing sacrificial hydrogen acceptors in alkane dehydrogenation catalysis, electrochemical methods for oxidative activation of a pincer-ligated iridium hydride intermediate were explored. A 1H(+)/2e(-) oxidation process was observed in THF solvent, with net hydride loss leading to a reactive cationic intermediate that can be trapped by chloride. Analogous reactivity was observed with the concerted hydride transfer reagent Ph3C(+), connecting chemical and electrochemical hydride loss pathways.

A prospective multicentre observational study of adverse iatrogenic events and substandard care preceding intensive care unit admission (PREVENT).

We examined the current incidence, type, severity and preventability of iatrogenic events associated with intensive care unit admission in five hospitals in England. All unplanned adult admissions to intensive care units were prospectively reviewed over a continuous six-week period. In the week before admission, 76/280 patients (27%) experienced 104 iatrogenic events. The majority of iatrogenic events were categorised as medical (37%), drug (17%) or nursing events (17%). Seventy-seven per cent of the events were considered preventable and 80% caused or contributed to admission. Eleven events were thought to have contributed to a patient's death. The mean (SD) age of patients who had an event was greater (63 (21) years) than those who had not (57 (19) years, p = 0.023), and they had a longer median (IQR [range]) intensive care stay, 4 (1-8 [0-29]) days vs 3 (1-5 [0-20]) days, respectively, p = 0.043.

Patients with faecal peritonitis admitted to European intensive care units: an epidemiological survey of the GenOSept cohort.

INTRODUCTION: Faecal peritonitis (FP) is a common cause of sepsis and admission to the intensive care unit (ICU). The Genetics of Sepsis and Septic Shock in Europe (GenOSept) project is investigating the influence of genetic variation on the host response and outcomes in a large cohort of patients with sepsis admitted to ICUs across Europe. Here we report an epidemiological survey of the subset of patients with FP. OBJECTIVES: To define the clinical characteristics, outcomes and risk factors for mortality in patients with FP admitted to ICUs across Europe. METHODS: Data was extracted from electronic case report forms. Phenotypic data was recorded using a detailed, quality-assured clinical database. The primary outcome measure was 6-month mortality. Patients were followed for 6 months. Kaplan-Meier analysis was used to determine mortality rates. Cox proportional hazards regression analysis was employed to identify independent risk factors for mortality. RESULTS: Data for 977 FP patients admitted to 102 centres across 16 countries between 29 September 2005 and 5 January 2011 was extracted. The median age was 69.2 years (IQR 58.3-77.1), with a male preponderance (54.3%). The most common causes of FP were perforated diverticular disease (32.1%) and surgical anastomotic breakdown (31.1%). The ICU mortality rate at 28 days was 19.1%, increasing to 31.6% at 6 months. The cause of FP, pre-existing co-morbidities and time from estimated onset of symptoms to surgery did not impact on survival. The strongest independent risk factors associated with an increased rate of death at 6 months included age, higher APACHE II score, acute renal and cardiovascular dysfunction within 1 week of admission to ICU, hypothermia, lower haematocrit and bradycardia on day 1 of ICU stay. CONCLUSIONS: In this large cohort of patients admitted to European ICUs with FP the 6 month mortality was 31.6%. The most consistent predictors of mortality across all time points were increased age, development of acute renal dysfunction during the first week of admission, lower haematocrit and hypothermia on day 1 of ICU admission.

Sinonasal inverted papilloma involving the temporal bone via the eustachian tube: case report.

OBJECTIVE: This study reports a case of a sinonasal inverted papilloma with spread to the temporal bone via the eustachian tube and subsequent transformation to squamous cell carcinoma. METHOD: An 81-year-old woman presented with sinonasal inverted papilloma which subsequently spread to the ear. A literature review of inverted papilloma was carried out based on a Pubmed search of studies published between 1987 and 2011, using the key words 'sinonasal inverted papilloma', 'temporal bone inverted papilloma' and 'squamous cell carcinoma'. RESULTS AND CONCLUSION: Sinonasal and temporal bone inverted papillomas may sometimes be linked through direct spread via the eustachian tube. Inverted papillomas have the potential for malignant transformation; careful monitoring of both the nose and ear is therefore required for inverted papillomas found in the nasopharynx.

Rotary components, random ellipses and polarization: a statistical perspective.

Rotary analysis decomposes vector motions on the plane into counter-rotating components, which have proved particularly useful in the study of geophysical flows influenced by the rotation of the Earth. For stationary random signals, the motion at any frequency takes the form of a random ellipse. Although there are numerous applications of rotary analysis, relatively little attention has been paid to the statistical properties of the random ellipses or to the estimated rotary coefficient, which measures the tendency to rotate counterclockwise or clockwise. The precise statistical structure of the ellipses is reviewed, including the random behaviour of the ellipse orientation, aspect ratio and intensity. Special attention is then paid to spectral matrix estimation from physical data and to hypothesis testing and confidence intervals computed using the estimated matrices.

Brain connectivity in positive and negative syndrome schizophrenia.

If, as is widely believed, schizophrenia is characterized by abnormalities of brain functional connectivity, then it seems reasonable to expect that different subtypes of schizophrenia could be discriminated in the same way. However, evidence for differences in functional connectivity between the subtypes of schizophrenia is largely lacking and, where it exists, it could be accounted for by clinical differences between the patients (e.g. medication) or by the limitations of the measures used. In this study, we measured EEG functional connectivity in unmedicated male patients diagnosed with either positive or negative syndrome schizophrenia and compared them with age and sex matched healthy controls. Using new methodology (Medkour et al., 2009) based on partial coherence, brain connectivity plots were constructed for positive and negative syndrome patients and controls. Reliable differences in the pattern of functional connectivity were found with both syndromes showing not only an absence of some of the connections that were seen in controls but also the presence of connections that the controls did not show. Comparing connectivity graphs using the Hamming distance, the negative-syndrome patients were found to be more distant from the controls than were the positive syndrome patients. Bootstrap distributions of these distances were created which showed a significant difference in the mean distances that was consistent with the observation that negative-syndrome diagnosis is associated with a more severe form of schizophrenia. We conclude that schizophrenia is characterized by widespread changes in functional connectivity with negative syndrome patients showing a more extreme pattern of abnormality than positive syndrome patients.

Graphical modelling for brain connectivity via partial coherence.

Spectral and coherence methodologies are ubiquitous for the analysis of multiple time series. Partial coherence analysis may be used to try to determine graphical models for brain functional connectivity. The outcome of such an analysis may be considerably influenced by factors such as the degree of spectral smoothing, line and interference removal, matrix inversion stabilization and the suppression of effects caused by side-lobe leakage, the combination of results from different epochs and people, and multiple hypothesis testing. This paper examines each of these steps in turn and provides a possible path which produces relatively 'clean' connectivity plots. In particular we show how spectral matrix diagonal up-weighting can simultaneously stabilize spectral matrix inversion and reduce effects caused by side-lobe leakage, and use the stepdown multiple hypothesis test procedure to help formulate an interaction strength.

Differences in intracellular calcium homeostasis between atrial and ventricular myocytes.

The role that Ca(2+) plays in ventricular excitation contraction coupling is well defined and much is known about the marked differences in the spatiotemporal properties of the systolic Ca(2+) transient between atrial and ventricular myocytes. However, to date there has been no systematic appraisal of the Ca(2+) homeostatic mechanisms employed by atrial cells and how these compare to the ventricle. In the present study we sought to determine the fractional contributions made to the systolic Ca(2+) transient and the decay of [Ca(2+)](i) by the sarcoplasmic reticulum and sarcolemmal mechanisms. Experiments were performed on single myocytes isolated from the atria and ventricles of the rat. Intracellular Ca(2+) concentration, membrane currents, SR Ca(2+) content and cellular Ca(2+) buffering capacity were measured at 23 degrees C. Atrial cells had smaller systolic Ca(2+) transients (251+/-39 vs. 376+/-41 nmol x L(-1)) that decayed more rapidly (7.4+/-0.6 vs. 5.45+/-0.3 s(-1)). This was due primarily to an increased rate of SR mediated Ca(2+) uptake (k(SR), 6.88+/-0.6 vs. 4.57+/-0.3 s(-1)). SR Ca(2+) content was 289% greater and Ca(2+) buffering capacity was increased approximately 3-fold in atrial cells (B(max) 371.9+/-32.4 vs. 121.8+/-8 micromol x L(-1), all differences P<0.05). The fractional release of Ca(2+) from the SR was greater in atrial cells, although the gain of excitation contraction coupling was the same in both cell types. In summary our data demonstrate fundamental differences in Ca(2+) homeostasis between atrial and ventricular cells and we speculate that the increased SR Ca(2+) content may be significant in determining the increased prevalence of arrhythmias in the atria.

Relationship between lifting capacity and anthropometric measures.

STUDY DESIGN: Prospective analysis of relationship between lifting capacity and multiple anthropometric variables. OBJECTIVES: To determine the relationship between lifting capacity and anthropometric variables and to model this relationship quantitatively. BACKGROUND: Low-back injuries commonly occur in individuals who perform lifting tasks. Objective data are needed to determine preinjury lifting capacity that, in turn, might be used to guide decisions during rehabilitation of these injuries. METHODS AND MEASURES: We recorded age and sex and measured the following variables for 35 men and 23 women between the ages of 22 and 40: height, weight, percentage of body fat, torso height, pelvic width, pelvic girth, arm length, thigh girth, and calf girth. Variables were selected for the study on the basis of theoretical modeling or previous research regarding the relationship between study variables and lifting capacity. Subjects also were tested to determine their maximum lifting capacity by using a lordotic lumbar spine lifting technique. RESULTS: Stepwise regression analysis indicated that the combination of sex, age, thigh girth, pelvic girth, and percentage body fat was significantly related to maximum lift capacity (multiple R2 = 0.76). The mean absolute difference (+/- SD) between lifted amount predicted by the regression model and the actual amount lifted was 118.6 +/- 86 N (26 +/- 19.3 lb), which corresponded to an average absolute error of 16% (SD = 14%) of the actual weight lifted. CONCLUSION: The results may be useful in estimating 1 aspect of preinjury lifting capacity. Similar studies are needed to model the requirements of frequency of lift, duration of lifting efforts, variety of hand-object coupling, and combined lifting and reaching.

Genes expressed in Pinus radiata male cones include homologs to anther-specific and pathogenesis response genes.

We describe the isolation and characterization of 13 cDNA clones that are differentially expressed in male cones of Pinus radiata (D. Don). The transcripts of the 13 genes are expressed at different times between meiosis and microspore mitosis, timing that corresponds to a burst in tapetal activity in the developing anthers. In situ hybridization showed that four of the genes are expressed in the tapetum, while a fifth is expressed in tetrads during a brief developmental window. Six of the seven cDNAs identified in database searches have striking similarity to genes expressed in angiosperm anthers. Seven cDNAs are homologs of defense and pathogen response genes. The cDNAs identified are predicted to encode a chalcone-synthase-like protein, a thaumatin-like protein, a serine hydrolase thought to be a putative regulator of programmed cell death, two lipid-transfer proteins, and two homologs of the anther-specific A9 genes from Brassica napus and Arabidopsis. Overall, our results support the hypothesis that many of the reproductive processes in the angiosperms and gymnosperms were inherited from a common ancestor.

PRFLL--a Pinus radiata homologue of FLORICAULA and LEAFY is expressed in buds containing vegetative shoot and undifferentiated male cone primordia.

In angiosperms, the formation of the flower meristem is controlled by partially redundant flower meristem identity genes of which FLORICAULA (FLO)/LEAFY (LFY) plays a central role. It is not known whether formation of reproductive organs of pre-angiosperm species is similarly regulated. Recently, a FLO/LFY-like cDNA, NEEDLY (NLY), has been cloned in a conifer species Pinus radiata (D. Don). Here we report cloning of a different Pinus radiata FLO/LFY-like cDNA, PRFLL. PRFLL had two large regions of high similarity to angiosperm FLO/LFY orthologues: amino acids 61-126 and 247-406 (50% and 81% identity, and 75% and 88% similarity, respectively, to LFY) and shorter regions of local similarity. Overall identity was 53% to LFY and 61% to NLY. Phylogenetic analysis of deduced protein sequences including partial LFY-like sequences from Pseudotsuga menziesii indicated that conifer proteins constituted a separate clade that could be divided into two groups represented by NLY and PRFLL. In contrast to angiosperms, both conifers had two paralogous proteins resembling LFY. Northern hybridisation analysis revealed expression of PRFLL in vegetative buds of juvenile, adolescent and mature trees. The transcript was not detected in vascular cambium, roots or secondary needles. To follow PRFLL expression during the early stages of cone development we analysed a temporal series of buds containing cone primordia, and developing cones, using Northern hybridisation and confocal microscopy in parallel. PRFLL mRNA was detected in buds from dominant and subordinate branches, in which cone and shoot primordia develop, and in developing male cones but not in developing female cones. Expression was particularly high in buds containing axillary primordia prior to their differentiation as male cone primordia. This is consistent with PRFLL being involved in determination of the male cone primordium identity.

Stable transformation and regeneration of transgenic plants of Pinus radiata D. Don.

A biolistic particle delivery system was used to genetically transform embryogenic tissue of Pinus radiata. The introduced DNA contained a uidA reporter gene under the control of either the tandem CaMV 35S or the artificial Emu promoter, and the npt II selectable marker controlled by the CaMV 35S promoter. The average number of stable, geneticin-resistant lines recovered was 0.5 per 200 mg fresh weight bombarded tissue. Expression of the uidA reporter gene was detected histochemically and fluorimetrically in transformed embryogenic tissue and in derived mature somatic embryos and regenerated plants. The integration of uidA and npt II genes into the Pinus radiata genome was demonstrated using PCR amplification of the inserts and Southern hybridisation analysis. The expression of both genes in transformed tissue was confirmed by Northern hybridisation analysis. More than 150 transgenic Pinus radiata plants were produced from 20 independent transformation experiments with four different embryogenic clones.

Identification of a putative active site residue in the exo-beta-(1,3)-glucanase of Candida albicans.

Recombinant exo-beta-(1,3)-glucanase from Candida albicans was expressed in Saccharomyces cerevisiae and purified. The enzyme contains a number of short blocks of sequence homology with several genes for cellulases of the family A glucanases including the conserved sequence motif NEP which has previously been shown to be important in the catalytic function of several cellulases. Site directed mutagenesis of this glutamic acid residue in the 1,3 glucanase (E230D, E230Q) decreased the enzymatic activity 15,000- and 400-fold, respectively. This suggests that the E of the NEP participates in catalysis of the exoglucanase and other related glucanases.