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Background: Spinocerebellar ataxia type 12 (SCA12) is a rare form of an autosomal-dominant ataxic disorder associated with an expansion of CAG repeat length. Here, we present a large case series of patients with SCA12 and describe a wide range of typical and rare symptoms. Methods: Twenty-one consecutive patients with genetically proven SCA12 underwent detailed neurological examination. We assessed clinical characteristics using validated rating scales for evaluating motor features in SCA. Nonmotor symptoms and quality of life were assessed using appropriate, validated scales. Correlations of CAG repeat length with both severity score and age of onset were explored. Results: The mean age of onset was 51 years, and most patients were descendants of a single, endogamous Indian community (Agarwal). Tremor was the most common initial presenting symptom (90%). Hand dystonia was present in 14 of 21 patients, and most patients in the cohort presented with gait disturbance. Neuropsychiatric manifestations were common coexisting features. The CAG repeat length was significantly correlated (r = À0.760; P = 0.0001) with early age of onset, but not with disease severity. Tremor affected the quality of life in 18 of 21 patients, because they had difficulty in handling liquids. Conclusions: Tremor was the most common, nonataxic symptom at initial presentation in patients with SCA12. Proximal upper limb tremor, typically with high amplitude and low frequency, can raise a strong diagnostic suspicion. Associated hand dystonia was a common coexisting motor feature. Various nonmotor features were also observed in several cases which require therapeutic attention.

Background In the west, survival following treatment of childhood acute lymphoblastic leukaemia (ALL) approaches 90%. Outcomes in India do not exceed 70%. To address this disparity, the Indian Collaborative Childhood Leukaemia group (ICiCLe) developed in 2013 a contemporary treatment protocol for uniform risk-stratified management of first presentation ALL based on cytogenetics and minimal residual disease levels (MRD). A multicentre randomised clinical trial opened in 2016 (ICiCLe-ALL-14) and examines the benefit of randomised interventions to decrease toxicity and improve outcomes. Methods Patients 1–18 years with newly diagnosed ALL are categorised into four risk groups based on presentation features, tumour genetics and treatment response. Standard risk includes young (< 10 years) B cell precursor ALL (BCP-ALL) patients with low presentation leucocyte count (< 50 × 109/L) and no high-risk features. Intermediate risk includes BCP-ALL patients with no high-risk features but are older and have high presentation leucocyte counts and/or bulky disease. High risk includes BCP-ALL patients with any high-risk feature, including high-risk genetics, central nervous system leukaemia, poor prednisolone response at treatment day 8 and high MRD (≥ 0·01%) at the end of induction. Patients with T-lineage ALL constitute the fourth risk group. All patients receive four intensive treatment blocks (induction, consolidation, interim maintenance, delayed intensification) followed by 96 weeks of maintenance. Treatment intensity varies by risk group. Clinical data management is based on a web-based remote data capture system. The first randomisation examines the toxicity impact of a shorter induction schedule of prednisolone (3 vs 5 weeks) in young non-high-risk BCP-ALL. The second randomisation examines the survival benefit of substituting doxorubicin with mitoxantrone in delayed intensification for all patients. Primary outcome measures include event-free survival (overall, by risk groups), sepsis rates in induction (first randomisation) and event-free survival rates following second randomisation. Discussion ICiCLe-ALL-14 is the first multicentre randomised childhood cancer clinical trial in India. The pre-trial phase allowed standardisation of risk-stratification diagnostics and established the feasibility of collaborative practice, uniform treatment, patient enrolment and data capture. Pre-trial observations confirm the impact of risk-stratified therapy in reducing treatment-related deaths and costs. Uniform practice across centres allows patients to access care locally, potentially decreasing financial hardship and dislocation. Trial registration Clinical Trials Registry-India (CTRI) CTRI/2015/12/006434. Registered on 11 December 2015

Increased morbidity owing to P. vivax malaria was observed and risk of mortality was highest in patients with ARDS and MODS.

Objectives: The usual radical radiotherapy treatment prescribed for head and neck squamous cell carcinoma (HNSCC) is 70 Gy (in 2 Gy per fraction equivalent) administered to the high-risk target volume (TV). This can be planned using either a forward-planned photon-electron junction technique (2P) or a single-phase (1P) forward-planned technique developed in-house. Alternatively, intensity-modulated radiotherapy (IMRT) techniques, including helical tomotherapy (HT), allow image-guided inversely planned treatments. This study was designed to compare these three planning techniques with regards to TV coverage and the dose received by organs at risk. Methods: We compared the dose-volume histograms and conformity indices (CI) of the three planning processes in five patients with HNSCC. The tumour control probability (TCP), normal tissue complication probability (NTCP) and uncomplicated tumour control probability (UCP) were calculated for each of the 15 plans. In addition, we explored the radiobiological rationality of a dose-escalation strategy. The TCP for CTV1 with HT were 79.2%, 85.2%, 81.1%, 83.0% and 53.0%; for single-phase forward-planned technique, 76.5%, 86.9%, 73.4%, 81.8% and 31.8% and for the two-phase technique, 38.2%, 86.2%, 42.7%, 0.0% and 3.4%. Dose escalation using HT confirmed the radiobiological advantage in terms of TCP. Conclusion: TCP for the single-phase plans was comparable to that of HT plans, whereas that for the two-phase technique was lower. Centres that cannot provide IMRT for the radical treatment of all patients could implement the single-phase technique as standard to attain comparable TCP. However, IMRT produced better UCP, thereby enabling the exploration of dose escalation.

Background & Aims: Autoimmune pancreatitis (AIP) is a fibroinflammatory condition affecting the pancreas and could present as a multisystem disorder. Diagnosis and management can pose a diagnostic challenge in certain groups of patients. We report our experience of managing this condition in a tertiary pancreaticobiliary centre in the North East of England.Methods: Patients were identified from a prospectively maintained database of patients diagnosed with AIP between 2005 and 2013. Diagnosis of definite/probable AIP was based on the revised HISORt criteria. When indicated, patients were treated with steroids and relapses were treated with azathioprine. All patients have been followed up to date.Results: Twenty-two patients were diagnosed with AIP during this period. All patients had pancreatic protocol CT performed while some patients had either MR or EUS as part of the work up. Fourteen out of 22 (64%) had an elevated IgG4 level (mean: 10.9 g/L; range 3.4 - 31 g/L). Four (18%) patients underwent surgery. Extrapancreatic involvement was seen in 15 (68%) patients, with biliary involvement being the commonest. Nineteen (86%) were treated with steroids and five (23%) required further immunosuppression for treatment of relapses. The mean follow up period was 36.94 months (range 7 - 94).Conclusion: Autoimmune pancreatitis is being increasingly recognized in the British population. Extrapancreatic involvement, particularly extrahepatic biliary involvement seems to be a frequent feature.Diagnosis should be based on accepted criteria as this significantly reduces the chances of overlooking malignancy. Awareness of this relatively rare condition and a multi-disciplinary team approach will help us to diagnose and treat this condition more efiectively thereby reducing unnecessary interventions.

Several biotic (bacterial and viral pathogenesis) and abiotic stress factors like salt, drought, cold, and extreme temperatures significantly reduce crop productivity and grain quality throughout the world. MicroRNAs (miRNAs) are small (~22 nucleotides) non-coding endogenous RNA molecules which negatively regulate gene expression at the post-transcriptional level either by degrading the target protein-coding mRNA genes or suppressing translation in plants. Dirigent (DIR) gene protein plays a crucial role as they are involved to dictate the stereochemistry of a compound synthesized by other enzymes as well as in lignifications against biotic and abiotic stress. In plants, several miRNAs, as well as their targets, are known to regulate stress response but systematic identification of the same is limited. The present work has been designed for in silico identification of miRNAs against a total of sixty-one DIR genes in Oryza sativa Indica followed by target prediction of identified miRNAs through the computational approach and thereafter validation of potential miRNAs in rice genotypes. We systematically identified 3 miRNA and their respective DIR specific target gene in Oryza sativa Indica. The expression of these three miRNAs and their respective DIR specific targets were validated in rice seedlings subjected to five different abiotic stress conditions (heavy metal, high temperature, low temperature, salinity and drought) by quantitative Real-Time PCR (qRT-PCR). Expression analysis indicated that miRNA under stress conditions regulates the gene expression of the DIR gene in rice. To the best of our knowledge this is this is the first report in any organism showing the expression of ath-miRf10317-akr, and osamiRf10761-akr miRNAs in response to various abiotic stresses.

Objective: Intensity-modulated radiotherapy (IMRT) is increasingly being used to treat head and neck cancer cases. Methods: We discuss the clinical challenges associated with the setting up of an image guided intensity modulated radiotherapy service for a subset of head and neck cancer patients, using a recently commissioned helical tomotherapy (HT) Hi Art (Tomotherapy Inc, WI) machine in this article. We also discuss the clinical aspects of the tomotherapy planning process, treatment and image guidance experiences for the first 10 head and neck cancer cases. The concepts of geographical miss along with tomotherapy-specific effects, including that of field width and megavoltage CT (MVCT) imaging strategy, have been highlighted using the first 10 head and neck cases treated. Results: There is a need for effective streamlining of all aspects of the service to ensure compliance with cancer waiting time targets. We discuss how patient toxicity audits are crucial to guide refinement of the newly set-up planning dose constraints. The advantages of intensity-modulated radiotherapy (IMRT) in head and neck cancer, in terms of target conformation, organ at risk sparing and associated improvement in quality of life, and the potential for dose escalation, have been well documented [1][2][3]. The development and commercial release of the helical tomotherapy (HT) Hi Art (Tomotherapy, Madison WI) system by Mackie et al [4] has introduced advanced helical IMRT delivery techniques and combined these with integrated onboard image guidance capabilities [5]. Recent adoption of this technology within the NHS by two centres (Cambridge and Newcastle), alongside existing provision within a private sector treatment centre (BUPA Cromwell Hospital, London), enables delivery of highly conformal image-guided IMRT in the UK.The physical characteristics of the HT system are described in detail elsewhere [4,5]; however, in basic terms, the system is a short waveguide 6 MV linac mounted on a spiral CT gantry system. Beam collimation is by a pneumatically controlled binary multileaf collimator (MLC), with each leaf projecting to 6.25 mm at isocentre, for three selectable field widths [6]. Owing to its continuous rotational delivery technique and rapid beam modulation throughout its full arc of travel, the HT system gives greater flexibility than conventional linear accelerator (linac)-based IMRT that provides intensity modulation at multiple fixed gantry angles. Planning comparisons between tomotherapy and rotational techniques using conventional linacs, volumetric arc therapy (VMAT) or intensity-modulated arc therapy (IMAT), have also been published [7,8]; however, there is ongoing debate as to the relative merits of each technique [9][10][11][12].The complexity of head and neck radiotherapy is due to the proximity of multiple organs at risk (OAR), including critical structures such as the brain stem and spinal cord and important functional organs such as the parotid glands, optic nerve, optic chiasm, larynx and mandible. The dose prescription ...