Diabetic ketoacidosis in an adolescent and young adult population in the UK in 2014: a national survey comparison of management in paediatric and adult settings:Special Issue on Diabetes and Childhood

Aims: To assess the management of diabetic ketoacidosis in young people, which differs in the UK between paediatric and adult services, and to evaluate outcomes and extent to which national guidelines are used. Methods: A standardized questionnaire was sent to all paediatric and adult diabetes services in England, requesting details of all diabetic ketoacidosis admissions in young people aged > 14 years in paediatric services (‘paediatric’ patients), and in young adults up to the age of 22 years in adult services (‘adult’ patients). Results: A total of 64 adult patients aged ≤ 22 years (mean age 19.2 years) were reported, of whom seven were aged between 10 and 16 years. A total of 71 paediatric patients were reported [mean (range) age 14.9 (11–18) years]. We found that 85% of paediatric and 69% of adult patients were treated according to national guidelines, 99% of paediatric and 89% of adult patients were treated with 0.9% saline and fixed-rate insulin infusions and 16% of adult patients received an insulin bolus. Insulin treatment was initiated later in paediatric patients than in adult patients (100 vs 39 min; P < 0.001). In 23% of adult patients and 8.8% of paediatric patients, potassium levels were < 3.5 mmol/l (P < 0.005). The lowest mean potassium levels were 3.8 mmol/l in paediatric and 3.5 mmol/l in adult patients (P < 0.005). Hypoglycaemia occurred in 42.3% of paediatric and 36% of adult patients. Time to resolution was similar in paediatric and adult patients (16.0 vs 18.2 h), as was duration of hospital stay (2.35 vs 2.53 days). Conclusions: Young people were treated according to national guidelines, but the quality of monitoring was variable in both paediatric and adult settings. The incidence of hypoglycaemia and hypokalaemia was unacceptably high

The challenges of managing breast cancer in the developing world- a perspective from sub- Saharan Africa

PKCommunicable diseases are the major cause of mortality in lower-income countries. Consequently, local and international resources are channelled mainly into addressing the impact of these conditions. HIV, however, is being successfully treated, people are living longer, and disease patterns are changing. As populations age, the incidence of cancer inevitably increases. The World Health Organization has predicted a dramatic increase in global cancer cases during the next 15 years, the majority of which will occur in low- and middle-income countries. Cancer treatment is expensive and complex and in the developing world 5% of global cancer funds are spent on 70% of cancer cases. This paper reviews the challenges of managing breast cancer in the developing world, using sub-Saharan Africa as a model

Voluntary activation failure is detectable in some myositis patients with persisting quadriceps femoris weakness: an observational study

This cross-sectional, observational study was undertaken to examine whether voluntary activation failure could contribute to the persisting weakness observed in some patients with treated idiopathic inflammatory myositis. In 20 patients with myositis of more than six months' duration (5 males, 15 females; mean [± 1 SD] age 53 [11] years) and 102 normal subjects (44 males, 58 females; mean age 32 [8] years), isometric maximum voluntary contractions (MVCs) of the dominant quadriceps femoris (QF) were quantified. Absolute MVC results of normal subjects and patients were then normalised with respect to lean body mass (force per units of lean body mass), giving a result in Newtons per kilogram. Based on mass-normalised force data of normal subjects, patients were arbitrarily stratified into "weak" and "not weak" subgroups. During further MVC attempts, the "twitch interpolation" technique was used to assess whether the QF voluntary activation of patients was complete. This technique relies on the fact that, because muscle activation is incomplete during submaximal voluntary contractions, electrical stimulation of the muscle can induce force increments superimposed on the submaximal voluntary force being generated. No between-gender differences were seen in the mass-normalised MVC results of healthy subjects, so the gender-combined results of 6.6 (1.5) N/kg were used for patient stratification. No between-gender difference was found for mass-normalised MVCs in patients: males 5.4 (3.2) and females 3.0 (1.7) N/kg (p > 0.05). Mass-normalised MVCs of male patients were as great as those of normal subjects (p > 0.05), but mass-normalised MVCs of female patients were significantly smaller than those of the normal subjects (p < 0.001). Only one of the six "not weak" patients exhibited interpolated twitches during electrical stimulation, but six of the 14 "weak" patients did, the biggest twitches being seen in the weakest patient. That interpolated twitches can be induced in some myositis patients with ongoing QF weakness during supposed MVCs clearly suggests that voluntary activation failure does contribute to QF weakness in those patients

Activation and modulation of recombinant glycine and GABAA receptors by 4-halogenated analogues of propofol

BACKGROUND AND PURPOSE: Glycine receptors are important players in pain perception and movement disorders, and therefore an important therapeutic target. Glycine receptors can be modulated by the intravenous anesthetic propofol (2,6-diisopropylphenol); however, the drug is more potent, by at least one order of magnitude, on GABAA receptors. It has been proposed that halogenation of the propofol molecule generates compounds with selective enhancement of glycinergic modulatory properties. EXPERIMENTAL APPROACH: We synthesized 4-bromopropofol, 4-chloropropofol, and 4-fluoropropofol. The direct activating and modulatory effects of these drugs and propofol were compared on recombinant rat glycine and human GABAA receptors expressed in oocytes. Behavioral effects of the compounds were compared in the tadpole loss-of-righting assay. KEY RESULTS: The concentration-response curves for potentiation of homomeric α1, α2, and α3 glycine receptors were shifted to lower drug concentrations by 2-10-fold for the halogenated compounds. Direct activation by all compounds was minimal with all subtypes of the glycine receptor. The four compounds were essentially equally potent modulators of the α1β3γ2L GABAA receptor with EC50 s between 4 and 7 μM. The EC50 s for loss-of-righting in Xenopus tadpoles, a proxy for loss of consciousness and considered to be mediated by actions on GABAA receptors, ranged from 0.35 to 0.87 μM. Conclusions and Implications We confirm that halogenation of propofol more strongly affects modulation of homomeric glycine receptors than α1β3γ2L GABAA receptors. However, the effective concentrations of all tested halogenated compounds remained lower for GABAA receptors. We infer that 4-bromo-, 4-chloro, or 4-fluoropropofol are not selective homomeric glycine receptor modulators

The predictive and prognostic potential of plasma telomerase reverse transcriptase (TERT) RNA in rectal cancer patients

Background: Preoperative chemoradiotherapy (CRT) followed by surgery is the standard care for locally advanced rectal cancer, but tumour response to CRT and disease outcome are variable. The current study aimed to investigate the effectiveness of plasma telomerase reverse transcriptase (TERT) levels in predicting tumour response and clinical outcome. Methods: 176 rectal cancer patients were included. Plasma samples were collected at baseline (before CRT\ubcT0), 2 weeks after CRT was initiated (T1), post-CRT and before surgery (T2), and 4\u20138 months after surgery (T3) time points. Plasma TERT mRNA levels and total cell-free RNA were determined using real-time PCR. Results: Plasma levels of TERT were significantly lower at T2 (Po0.0001) in responders than in non-responders. Post-CRT TERT levels and the differences between pre- and post-CRT TERT levels independently predicted tumour response, and the prediction model had an area under curve of 0.80 (95% confidence interval (CI) 0.73\u20130.87). Multiple analysis demonstrated that patients with detectable TERT levels at T2 and T3 time points had a risk of disease progression 2.13 (95% CI 1.10\u20134.11)-fold and 4.55 (95% CI 1.48\u201313.95)-fold higher, respectively, than those with undetectable plasma TERT levels. Conclusions: Plasma TERT levels are independent markers of tumour response and are prognostic of disease progression in rectal cancer patients who undergo neoadjuvant therapy

Correction to: Do pain, anxiety and depression influence quality of life for people with amyotrophic lateral sclerosis/motor neuron disease? A national study reconciling previous conflicting literature.

The original version of this article unfortunately contained a mistake. Oliver Hanemann name was incorrect in the in the acknowledgements section of this paper

Prediction of the radiative heat transfer in small and large scale oxy-coal furnaces

Predicting thermal radiation for oxy-coal combustion highlights the importance of the radiation models for the spectral properties of gases and particles. This study numerically investigates radiation behaviours in small and large scale furnaces through refined radiative property models, using the full-spectrum correlated k (FSCK) model and Mie theory based data, compared with the conventional use of the weighted sum of grey gases (WSGG) model and the constant values of the particle radiation properties. Both oxy-coal combustion and air-fired combustion have been investigated numerically and compared with combustion plant experimental data. Reasonable agreements are obtained between the predicted results and the measured data. Employing the refined radiative property models achieves closer predicted heat transfer properties to the measured data from both furnaces. The gas-phase component of the radiation energy source term obtained from the FSCK property model is higher within the flame region than the values obtained by using the conventional methods. The impact of using non-grey radiation behaviour of gases through the FSCK is enhanced in the large scale furnace as the predicted gas radiation source term is approximately 2-3 times that obtained when using the WSGG, while the same term is in much closer agreement between the FSCK and the WSGG for the pilot-scale furnace. The predicted total radiation source term (from both gases and particles) is lower in the flame region after using the refined models, which results in a hotter flame (approximately 50-150 K higher in this study) compared with results obtained from conventional methods. In addition, the predicted surface incident radiation reduces by using the refined radiative property models for both furnaces, in which the difference is relevant with the difference in the predicted radiation properties between the two modelling techniques. Numerical uncertainties resulting from the influences of combustion model, turbulent particle dispersion and turbulence modelling on the radiation behaviours are discussed