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The generation of clinical good manufacturing practices (GMP)-grade adeno-associated virus (AAV) vectors requires purification strategies that support the generation of vectors of high purity, and that exhibit a good safety and efficacy profile. To date, most reported purification schemas are serotype dependent, requiring method development for each AAV gene therapy product. Here, we describe a platform purification process that is compatible with the purification of multiple AAV serotypes. The method generates vector preparations of high purity that are enriched for capsids with full vector genomes, and that minimizes the fractional content of empty capsids. The two-column purification method, a combination of affinity and ion exchange chromatographies, is compatible with a range of AAV serotypes generated by either the transient triple transfection method or the more scalable producer cell line platform. In summary, the adaptable purification method described can be used for the production of a variety of high-quality AAV vectors suitable for preclinical testing in animal models of diseases. Keywords: AAV purification, epitope swapping, analytical ultracentrifugation

Paediatrics as a speciality has previously been a red outlier for the feedback category within the annual GMC training survey. This suggests that trainees at least, feel that feedback within their training is insufficient. We wished to assess perceptions of feedback and identify both real and perceived barriers to successful feedback by sampling current trainees and supervisors within the Severn Deanery on their experiences. The topic was introduced at a workshop during the Severn Deanery Paediatric Conference in 2016. Copies of the trainee questionnaire were distributed and subsequently an online version was sent via deanery email and the Severn Paediatrics Facebook group. Trainers were surveyed via an online form disseminated via email. We had a response rate of 65% for the trainee survey and 40% for the trainers’ survey. 72% of trainees reported feeling that they did not receive enough feedback, with several recurring themes identified, including lack of time, workload and staff shortages. This was also reflected in the trainers’ survey but additionally the perception of feedback was cited as an issue, with trainees not always able to recognise ‘feedback’ in more informal situations, leading to a mismatch between the amount trainers felt was given versus the amount trainees acknowledged. 83% of trainees wanted feedback integrated into daily practice, however only 34% of trainers felt that daily feedback was necessary. There was concern over trainee resilience and the ability to give constructive feedback to trainees; ‘It does seem ‘unfair’ when they are busting a gut to keep the show on the road to give them any kind of negative feedback’, however a recurring theme from trainees was to reduce the perceived stress of feedback by increasing its regularity; ‘ I think this should be normalised, i.e. recognising that there are always things we could do better, it’s not a criticism’. The barriers we identified to regular feedback are well recognised within current medical training. However, our responses suggest a cultural issue within paediatrics regarding the perceived resilience of paediatric trainees. Our next step is to challenge the culture of feedback locally to improve clinical training within our region.

This study ‘Demand for and experiences with financial products and services’ describes and discusses the results of a survey to provide a first insight into the financial services that the smallholder farmers from climate smart villages use and to explore how these are related to climate smart agricultural technologies & practices. The study is one of three preliminary studies of a multi-year international research project (2016-2022) on ‘Business models, incentives and innovative finance for scaling climate smart agriculture (CSA)’. The knowledge and insights developed are used to further support ongoing and emerging climate smart projects in which CCAFS is involved. A survey was conducted to identify smallholder farmers and the small to medium enterprises (in different stages of the value chain) and their demand for and experiences with financial products and services. There were 148 respondents from 24 villages from Latin America, West Africa, East Africa, Southeast Asia and South Asia. The targeted number of female respondents (50%) was nog met in all regions, for example in India where the role of female farmers in irrigated agriculture would be limited. A limitation to the results is that in different regions a different number of villages was involved, making it more difficult to generalise results. Sometimes it would prove challenging to make conclusions about the reasoning behind the answers. The study is about adoption climate smart agriculture, but does not define the extent of adoption. ..

Aim To determine the etiological association, neurodevelopmental sequelae and role of Magnetic Resonance Imaging (MRI) in term newborn infants with seizures. Methods Cohort study of infants >37 weeks gestation delivered in a single level 3 centre in the UK from 1/12/2004 to 31/10/2009 (59 months), prospectively identified by a perinatal morbidity surveillance system and followed longitudinally for 18–24 months. Results 77 infants were identified with seizures during the study period (3.0/1000 live births). 9 infants died (12%). 73/77 (95%) had an aEEG recording and 70/77 (91%) had an MRI scan. In 95% of cases an underlying cause of seizures was elucidated. The most common diagnosis was HIE (65%) with neonatal stroke as the second most common diagnosis (12%). Overall, 28/77 (36%) of the cohort had a neurodevelopmental impairment (NDI), ranging from mild to severe. 37/50 infants with HIE (74%) received therapeutic hypothermia and 9 (24%) had NDI. Of the remaining 13 managed with normothermia, 4 had NDI (31%). NDI was prevalent in those with a diagnosis other than HIE (15/27; 56%), in particular stroke, hypoglycaemia and cerebral dysgenesis. 15/77 (19%) had recurrence of seizure in the first 2 years of life. The highest risk of seizure recurrence was in cerebral dysgenesis, hypoglycaemia and stroke. Infants with HIE had a very low risk of seizure recurrence (1/50; 2%). 45/70 (64%) had abnormal MRI findings. The negative predictive value of a normal MRI in survivors of developing any disability was 0.93. Conclusion This is the first report of a cohort of term infants with seizures fully investigated by MRI and aEEG. HIE was the most common cause of seizures in this population. Neonatal stroke was the most likely diagnosis for term infants presenting with seizures on day two of life. The universal use of MRI allows a cause to be identified in 95% of term infants with seizures. A normal MRI scan was highly predictive of a normal neurodevelopmental outcome. There was significant risk of NDI and seizure recurrence, particularly in those with a diagnosis other than HIE, supporting formal neurological surveillance.

Despite recent advances in the investigation and the imaging of the alimentary tract, the cause of some cases of gastrointestinal haemorrhage still remains obscure. A case of haemorrhage from a chronic volvulus of the terminal ileum is described, where standard investigations failed to demonstrate the site of bleeding. A barium follow-through showed a variable dilatation of the terminal ileum, at times resembling a diverticulum or duplication. A girl aged six and a half presented with a 1-year history of fatigue, recurrent abdominal pain and possible rectal bleeding. Her haemoglobin was 4.7 g/dl and she was transfused. She was readmitted within one month with a haemoglobin of 5.1 g/dl and was transfused again. Iron deficiency was confirmed by a low serum iron and bone marrow aspiration. Her biochemistry, red cell fragility and G6 PD levels were normal.

To the Editor:— In the London letter inThe Journal, January 20, page 266, under the title "Control of Venereal Disease in the War," is set out what purports to be a statement of the present policy of the British army authorities. This letter appears to be an extract of an article which appeared in the Lancet , Nov. 18, 1939, in which the author gave details of the policy of Ruritania toward venereal disease. In fact, the methods now employed in the British army do not include such things as arsphenamine injections three times a week, the use of liposoluble bismuth or the issue of leaflets on venereal disease to troops before they leave England. In addition, prophylaxis is not compulsory, nor was Col. B. L. Ank ("Blank"!) lent to the army by the Ministry of Hygiene. I should be very grateful, therefore, if you would take the earliest opportunity

I have lately noticed inThe Journalvarious articles on the use of ethyl chlorid as a short general anesthetic, and some specially constructed masks. To my mind the latter are too expensive for the general practitioner, and I desire to present a method that I use in the receiving ward of the Cincinnati Hospital. With the patient on his back, I place over his mouth and nose two layers of thin gauze. Over this I place a tin or glass funnel around the bottom of which is wrapped a towel, as shown in the accompanying illustration. The ethyl chlorid is sprayed down the small end of the funnel. The gauze keeps the nose from being frozen, and the towel prevents too great a loss of ethyl chlorid, yet gives free access of air, so that the vapor can not be too concentrated. The patient readily goes to sleep. The

Any laboratory worker who has had any amount of blood work to do, especially in making differential leucocyte counts, has been more or less troubled with the necessity of having to figure out the percentages of the various types of cells and the liability of error. The accompanying chart I have devised for use in the laboratory of the Cincinnati Hospital, and we have found it quite convenient in simplifying the work and removing sources of error. The chart is inexpensive and can be made out of a piece of ground glass or a slate, suitably ruled and marked in ink so as to be permanent. The temporary markings are made in pencil, can be readily erased, and the chart is again ready for service. It is figured out on a basis of a count of two hundred leucocytes, and marked on the left to designate the various types of cells, as