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Purpose To describe a series of children with extensive PNF or treatment refractory PLGG treated on a compassionate basis with trametinib. Methods We report on six patients with NF‐1 treated with trametinib on a compassionate basis at British Columbia Children's Hospital since 2017. Data were collected retrospectively from the patient record. RAPNO and volumetric criteria were used to evaluate the response of intracranial and extracranial lesions, respectively. Results Subjects were 21 months to 14 years old at the time of initiation of trametinib therapy and 3/6 subjects are male. Duration of therapy was 4–28 months at the time of this report. All patients had partial response or were stable on analysis. Two patients with life‐threatening PNF had a partial radiographic response in tandem with significant clinical improvement and developmental catch up. One subject discontinued therapy after 6 months due to paronychia and inadequate response. The most common adverse effect (AE) was grade 1–2 paronychia or dermatitis in 5/6 patients. There were no grade 3 or 4 AEs. At the time of this report, five patients remain on therapy. Conclusion Trametinib is an effective therapy for advanced PNF and refractory PLGG in patients with NF‐1 and is well tolerated in children. Further data and clinical trials are required to assess tolerance, efficacy and durability of response, and length of treatment required in such patients., Here, we report on response to Trametinib, a MEK inhibitor in children with NF‐1. Our experience presented in this report demonstrates that Trametinib is an effective therapy for advanced, life‐threatening PNF, and treatment‐refractory PLGG in patients with NF‐1 and is well tolerated in children.

The processing of instant coffee may involve pumping the material in a melt phase through operations at elevated pressures. The shear rheology of this material was investigated using the Cambridge multipass rheometer, which allows for shear rheometric testing under conditions of independently controlled temperature and pressure. In this work the back pressure was set to dissolve any air that was present in the melt, so that the rheology of the single phase material could be tested. Data were collected over the accessible range of conditions; shear rates from 0.01 to 1000 s −1 , temperatures from 80 to 110 °C, and pressures from 0.01 to 300 bar. The melt exhibited thixotropic behaviour at low shear rates, and the data could be fitted to a non-dimensionalised Carreau fluid model with a temperature dependence which followed an Andrade relationship. Sample to sample variation was observed, which is attributed to differing water content. The results demonstrate how the rheology of complex food materials can be accessed under process conditions., This work was supported by Mondelēz International, Jacob Douwe Egberts, and the Engineering and Physical Sciences Research Council.

Alexander Disease (AD) is a rare and ultimately lethal leukodystrophy, typically presenting in infants who exhibit developmental delay, macrocephaly, seizures, spasticity and quadriparesis. Classic infantile forms are generally due to sporadic mutations in GFAP that result in the massive deposition of intra-astrocytic Rosenthal fibres, particularly in the frontal white matter. However, phenotypic manifestations are broad and include both juvenile and adult forms that often display infratentorial pathology and a paucity of leukodystrophic features. We describe the unique case of an 8.5 year old female who presented with an 8 month history of progressively worsening vomiting and cachexia, whose extensive multidisciplinary systemic workup, including GI biopsies, proved negative. Neuroimaging ultimately revealed bilaterally symmetric and anterior predominant supratentorial signal alterations in the white matter plus a 1.7 x 1.2 x 0.7 mm right dorsal medullary mass. Biopsy of this presumed low-grade glioma revealed features in keeping with AD, which was later confirmed on whole exome sequencing. The proband exhibited a pathogenic p.Arg239Cys heterozygous missense mutation in GFAP, which was apparently inherited from her asymptomatic mother (1% mosaicism in the mother’s blood). Germline mosaic inheritance patterns of young-onset AD, particularly those presenting with a tumor-like mass of the brainstem, are scarcely reported in the literature and serve to expand the clinicopathologic spectrum of AD.LEARNING OBJECTIVESThis presentation with enable the learner to: 1.Recognize an uncommon clinical presentation of AD.2.Describe the underlying genetics of AD, including a rare familial juvenile onset form featuring germline mosaicism.

This paper details an investigation into the separation of Hexamethylenediamine (HMD) from dilute aqueous solutions by exploiting phase separation. HMD is a monomer used in the production of Nylon-6,6 and as such this separation is potentially useful in extracting purifying HMD produced from biological sources or reclaimed from waste made by the production of nylon. An investigation was undertaken into the effect of using sodium hydroxide (NaOH) to promote the phase separation, and a model was derived to predict this behaviour. Furthermore, the effect of various salts on this phase separation was investigated, and it was found that sodium sulphate and sodium carbonate promote the phase separation, but are unable to cause phase separation without the presence of sodium hydroxide.

When I arrived in New York thirty years ago, one of the first assignments I gave myself was to make sure to meet Mary Erler, an English professor at Fordham who had published an important article elucidating the care for books at Syon Abbey as it was described in the sacristan's account rolls of the early sixteenth century. Mary and I have stayed in touch ever since, sharing our common interest in Henry V's two great religious houses, that of Brigittine nuns and brothers at Syon, northwest across the Thames from Richmond Palace, and the Carthusian monastery of Jesus of Bethlehem at Sheen, on the southeast bank of the Thames, to the west of the palace grounds. Much of Mary's work has been on women's readership, spirituality, and associational networks (particularly through the medium of book production, ownership, gift, and bequest) in the later medieval and early modern period in England – with Syon Abbey as a constant thread in the web of her interests. A major part of my own interest has been in the production, transmission, and ownership of books among the later medieval English Carthusian monks – the nexus of textual, material, and social connection that the surviving manuscripts and early prints of these works embody – and the critical edition of some of the texts in these books. One of the strongest of these nexus of connection has been Syon Abbey; and the present paper is a study of the nexus of Syon Abbey and The Scale of Perfection , for there is a strong link between the two, a link formed in large part by the affective reading of the Scale by the nuns of Syon. Of the twenty-one surviving manuscripts originally containing the complete English text of the Scale , three have connections to Syon Abbey. These manuscripts are all affiliated with what I have termed the “Carthusian Group” of manuscripts of Scale II, although, to be fair, it could just as well have been given the somewhat more cumbersome title the “Carthusian-Brigittine Group.” This group comprises nine manuscripts and the 1494 Wynkyn de Worde editio princeps of the Scale ( STC 14042: all later printings in fact derive from this one), plus two manuscripts that represent conflation of the Carthusian group with some other. All manuscripts of the Carthusian group contain both books of the Scale .

OBJECTIVE Refractory symptomatic plexiform neurofibromas (PNF) and inoperable refractory low grade gliomas (LGG) pose a clinical challenge that may be life threatening. Phase 1 and 2 clinical trials of MEK inhibition with selumetinib in inoperable PNF and LGG have demonstrated promising results in pediatrics, however access has been limited to enrollment on clinical trial. Phase 1 clinical trial for trametinib a MEK 1 and 2 inhibitor has been completed, publication is pending. Thus we have treated a series of children on a compassionate basis with extensive PN or LGG refractory disease with trametinib, as this is available in Canada. METHODS We have treated children with trametinib on a compassionate basis in our province since 2017. Review of the clinical data regarding this therapy has been IRB approved. RESULTS Two young patients were treated for indication of life threatening extensive PNF and have had tumor shrinkage and improvement of clinical status. Treatment has been complicated by paronychiae, eczema exacerbation, chondrodermatitis nodularis helicis, RSV and influenza B infection and CTCAE grade 2 pneumonia. In spite of the side effects these two patients remain on treatment due to clear benefit from therapy including: improved respiratory compromise, hearing and dysphagia. We will present the data of additional patients treated with trametinib. CONCLUSION Trametinib is an effective therapy for life threatening PNF by changing the natural history of tumor growth in young children. Further data is required in terms of tolerance, efficacy and durability of response in such patients in the setting of clinical trials.

Nicholas Love was the prior of the Carthusian house of the Assumption of the Blessed Virgin Mary at Mount Grace from its incorporation into the Order at the General Chapter of 1410 until shortly before his death, which occurred between 15 March and 28 July, 1423. He is most commonly known to present-day scholarship as the author of The Mirror of the Blessed Life of Jesus Christ and because of the licensing of the Mirror by Archbishop Thomas Arundel in accordance with the stipulations of the Lambeth Constitutions of 1409, as an agent in the archbishop's campaign against the followers of John Wyclif, and against Wycliffite translation of the scriptures into the vernacular. It would be better, however, to see him as an actor in his own right, a promoter, like his continental European Carthusian confrères, of the reform of the western Church in the fifteenth century.

High-dose steroid administration is no longer recommended in the treatment of acute traumatic brain injury (TBI) as it failed to prove beneficial in improving patients’ outcome. However, a masked benefit of steroid administration in TBI management was that it provided corticosteroid replacement therapy in patients with TBI-related central adrenal insufficiency. We report the case of a 12-year-old boy who suffered a severe TBI from a motor vehicle accident that resulted in complete deficiency of anterior pituitary function. Central adrenal insufficiency was not ruled out by a near normal response to a low-dose ACTH test performed on D11. Consideration should be given to the empirical treatment of TBI pediatric patients with stress doses of corticosteroids if injury to the hypothalamus or pituitary gland is possible until a formal assessment of the hypothalamic—pituitary—adrenal axis can be made.

Background Creatine transporter (SLC6A8) deficiency is an X-linked inborn error of metabolism characterized by cerebral creatine deficiency, behavioral problems, seizures, hypotonia, and intellectual developmental disability. A third of patients are amenable to treatment with high-dose oral creatine, glycine, and L-arginine supplementation. Methods Given the limited treatment response, we initiated an open-label observational study to evaluate the effect of adjunct S-adenosyl methionine to further enhance intracerebral creatine synthesis. Results Significant and reproducible issues with sleep and behavior were noted in both male patients on a dose of 50/mg/kg. One of the two patients stopped S-adenosyl methionine and did not come for any follow-up. A safe and tolerable dose (17 mg/kg/day) was identified in the other patient. On magnetic resonance spectroscopy, this 8-year-old male did not show an increase in intracerebral creatine. However, significant improvement in speech/language skills, muscle mass were observed as well as in personal outcomes as defined by the family in activities related to communication and decision making. Discussion Further research is needed to assess the potential of S-adenosyl methionine as an adjunctive therapy for creatine transporter deficiency patients and to define the optimal dose. Our study also illustrates the importance of pathophysiology-based treatment, individualized outcome assessment, and patient/family participation in rare diseases research.