There is no market for new antibiotics: This allows an open approach to research and development

There is an increasingly urgent need for new antibiotics, yet there is a significant and persistent economic problem when it comes to developing such medicines. The problem stems from the perceived need for a 'market' to drive commercial antibiotic development. In this article, we explore abandoning the market as a prerequisite for successful antibiotic research and development. Once one stops trying to fix a market model that has stopped functioning, one is free to carry out research and development (R&D) in ways that are more openly collaborative, a mechanism that has been demonstrably effective for the R&D underpinning the response to the COVID pandemic. New 'open source' research models have great potential for the development of medicines for areas of public health where the traditional profit-driven model struggles to deliver. New financial initiatives, including major push/pull incentives, aimed at fixing the broken antibiotics market provide one possible means for funding an openly collaborative approach to drug development. We argue that now is therefore the time to evaluate, at scale, whether such methods can deliver new medicines through to patients, in a timely manner

A cross-sectional study of Victorian mobile intensive care ambulance paramedics knowledge of the Valsalva manoeuvre

<p>Abstract</p> <p>Background</p> <p>The Valsalva Manoeuvre (VM) is a primary measure for terminating haemodynamically stable supraventricular tachycardia (SVT) in the emergency care setting. The clinical use and termination success of the VM in the prehospital setting has not been investigated to date. The objective of this study was to determine Melbourne Mobile Intensive Care Ambulance (MICA) Paramedic knowledge of the VM, and to compare this understanding with an evidence-based model of VM performance.</p> <p>Methods</p> <p>A cross-sectional study in the form of a face-to-face interview was used to determine Melbourne MICA Paramedic understanding of VM instruction between January and February, 2008. The results were then compared with an evidence-based model of VM performance to ascertain compliance with the three criteria of position, pressure and duration. Ethics approval was granted.</p> <p>Results</p> <p>There were 28 participants (60.9%) who elected a form of supine posturing, some 23 participants (50%) selected the syringe method of pressure generation, with 16 participants (34.8%) selecting the "as long as you can" option for duration. On comparison, one out of 46 MICA Paramedics correctly identified the three evidence-based criteria.</p> <p>Conclusions</p> <p>The formal education of Melbourne's MICA Paramedics would benefit from the introduction of an evidence based model of VM performance, which would impact positively on patient care and may improve reversion success in the prehospital setting. The results of this study also demonstrate that an opportunity exists to promote the evidence-based VM criteria across the primary emergency care field.</p

Uniform approach to double shuffle and duality relations of various q-Analogs of multiple zeta values via Rota-Baxter algebras

The multiple zeta values (MZVs) have been studied extensively in recent years. Currently there exist a few different types of $q$-analogs of the MZVs ($q$-MZVs) defined and studied by mathematicians and physicists. In this paper, we give a uniform treatment of these $q$-MZVs by considering their double shuffle relations (DBSFs) and duality relations. The main idea is a modification and generalization of the one used by Castillo Medina et al. who have considered the DBSFs of a special type of $q$-MZVs. We generalize their method to a few other types of $q$-MZVs including the one defined by the author in 2003. With different approach, Takeyama has already studied this type by "regularization" and observed that there exist $\mathbb Q$-linear relations which are not consequences of the DBSFs. He also discovered a new family of relations which we call the duality relations in this paper. This deficiency of DBSFs occurs among other types, too, so we generalize the duality relations to all of these values and find that there are still some missing relations. This leads to the most general type of $q$-MZVs together with a new kind of relations called $\bf P$-$\bf Q$ relations which are used to lower the deficiencies further. As an application, we will confirm a conjecture of Okounkov on the dimensions of certain $q$-MZV spaces, either theoretically or numerically, for the weight up to 12. Some relevant numerical data are provided at the end

International Federation for Emergency Medicine model curriculum for medical student education in emergency medicine

There is a critical and growing need for emergency physicians and emergency medicine resources worldwide. To meet this need, physicians must be trained to deliver time-sensitive interventions and life-saving emergency care. Currently, there is no internationally recognized, standard curriculum that defines the basic minimum standards for emergency medicine education. To address this lack, the International Federation for Emergency Medicine (IFEM) convened a committee of international physicians, health professionals, and other experts in emergency medicine and international emergency medicine development to outline a curriculum for foundation training of medical students in emergency medicine. This curriculum document represents the consensus of recommendations by this committee. The curriculum is designed with a focus on the basic minimum emergency medicine educational content that any medical school should be delivering to its students during their undergraduate years of training. It is not designed to be prescriptive, but to assist educators and emergency medicine leadership in advancing physician education in basic emergency medicine content. The content would be relevant, not just for communities with mature emergency medicine systems, but also for developing nations or for nations seeking to expand emergency medicine within current educational structures. We anticipate that there will be wide variability in how this curriculum is implemented and taught, reflecting the existing educational milieu, the resources available, and the goals of the institutions’ educational leadership

The reliability and validity of three non-radiological measures of thoracic kyphosis and their relations to the standing radiological Cobb angle

UnlabelledHyperkyphosis is implicated in a mounting list of negative outcomes, including higher mortality. Hyperkyphosis research is hindered due to difficulties inherent in its measurement. By showing that three clinical measures of kyphosis are suitable for use in large scale, longitudinal, hyperkyphosis studies, we will facilitate much needed research in this field.IntroductionThe objective of this study is to describe the reliability of three non-radiological kyphosis measures (Debrunner kyphosis angle, flexicurve kyphosis index, and flexicurve kyphosis angle) and their validity compared to the Cobb angle and to approximate a Cobb angle from non-radiological kyphosis measures.MethodsWe analyzed data from 113 participants aged ≥ 60 years with kyphosis angle ≥ 40°. Cobb angle was measured on a standing lateral thoracolumbar radiograph using bounds at T4 and T12. Non-radiological measures of kyphosis were made three times by a single rater and a 4th time by a blinded second rater.ResultsIntra- and inter-rater reliabilities for non-radiological assessments were high (intra-class correlations of 0.96 to 0.98) and did not differ from each other. Pearson correlations, estimating validity, ranged from 0.62 to 0.69 and did not differ. The Debrunner angle was close to the Cobb angle, with scaling factor of 1.067 and an offset of 5°. The Flexicurve kyphosis angle had to be scaled by 1.53 to obtain the equivalent Cobb angle. The scaling factor for the Flexicurve kyphosis index to Cobb angle was 315, with an offset of 5°. Compared to the measured Cobb angle, Cobb angles predicted using the non-radiological measures had similar magnitude errors (standard deviations of the differences ranging between 10.24 and 11.26).ConclusionsEach non-radiological measurement had similar reliability and validity. Low cost, ease of use, and robustness to variations in spine contour argue for the Flexicurve in longitudinal kyphosis assessments. The approximate conversion factors provided will permit translation of non-radiological measures to Cobb angles

The Obligation of Physicians to Medical Outliers: A Kantian and Hegelian Synthesis

Background Patients who present to medical practices without health insurance or with serious co-morbidities can become fiscal disasters to those who care for them. Their consumption of scarce resources has caused consternation among providers and institutions, especially as it concerns the amount and type of care they should receive. In fact, some providers may try to avoid caring for them altogether, or at least try to limit their institutional or practice exposure to them. Discussion We present a philosophical discourse, with emphasis on the writings of Immanuel Kant and G.F.W. Hegel, as to why physicians have the moral imperative to give such outliers considerate and thoughtful care. Outliers are defined and the ideals of morality, responsibility, good will, duty, and principle are applied to the care of patients whose financial means are meager and to those whose care is physiologically futile. Actions of moral worth, unconditional good will, and doing what is right are examined. Summary Outliers are a legitimate economic concern to individual practitioners and institutions, however this should not lead to an evasion of care. These patients should be identified early in their course of care, but such identification should be preceded by a well-planned recognition of this burden and appropriate staffing and funding should be secured. A thoughtful team approach by medical practices and their institutions, involving both clinicians and non-clinicians, should be pursued

Alcohol affects neuronal substrates of response inhibition but not of perceptual processing of stimuli signalling a stop response

Alcohol impairs inhibitory control, including the ability to terminate an initiated action. While there is increasing knowledge about neural mechanisms involved in response inhibition, the level at which alcohol impairs such mechanisms remains poorly understood. Thirty-nine healthy social drinkers received either 0.4g/kg or 0.8g/kg of alcohol, or placebo, and performed two variants of a Visual Stop-signal task during acquisition of functional magnetic resonance imaging (fMRI) data. The two task variants differed only in their instructions: in the classic variant (VSST), participants inhibited their response to a “Go-stimulus” when it was followed by a “Stop-stimulus”. In the control variant (VSST_C), participants responded to the “Go-stimulus” even if it was followed by a “Stop-stimulus”. Comparison of successful Stop-trials (Sstop)>Go, and unsuccessful Stop-trials (Ustop)>Sstop between the three beverage groups enabled the identification of alcohol effects on functional neural circuits supporting inhibitory behaviour and error processing. Alcohol impaired inhibitory control as measured by the Stop-signal reaction time, but did not affect other aspects of VSST performance, nor performance on the VSST_C. The low alcohol dose evoked changes in neural activity within prefrontal, temporal, occipital and motor cortices. The high alcohol dose evoked changes in activity in areas affected by the low dose but importantly induced changes in activity within subcortical centres including the globus pallidus and thalamus. Alcohol did not affect neural correlates of perceptual processing of infrequent cues, as revealed by conjunction analyses of VSST and VSST_C tasks. Alcohol ingestion compromises the inhibitory control of action by modulating cortical regions supporting attentional, sensorimotor and action-planning processes. At higher doses the impact of alcohol also extends to affect subcortical nodes of fronto-basal ganglia- thalamo-cortical motor circuits. In contrast, alcohol appears to have little impact on the early visual processing of infrequent perceptual cues. These observations clarify clinically-important effects of alcohol on behaviour

Spontaneous intra-peritoneal bleeding secondary to warfarin, presenting as an acute appendicitis: a case report and review of literature

BACKGROUND: Warfarin is a coumarin anti-coagulant, used widely for the therapeutic and prophylactic anticoagulation. Although, it is considered as a life saving medicine, it is associated with the significant adverse effects including intra-abdominal bleeding, which have been very well documented in literature. However, the presentation of warfarin induced intra-peritoneal bleeding as an acute appendicitis has not been reported in English literature. We report this rare, spontaneous intra-peritoneal bleeding secondary to warfarin therapy, mimicking the signs and symptoms of an acute appendicitis for the first time in English literature. CASE PRESENTATION: A 41 year-old female patient who was on warfarin for prophylaxis following the previous episode of pulmonary embolism, presented to the Casualty with the typical symptoms of an acute appendicitis. During operative intervention, we found it to be the spontaneous intra-peritoneal bleeding secondary to warfarin. The patient recovered well following the operation. CONCLUSION: We recommend the use of the radiological investigations in all the cases of acute abdomen who are on warfarin even if the INR is within the therapeutic range