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.

We describe the case of an 11-month-old girl with a rare cerebellar glioblastoma driven by a NACC2-NTRK2 (Nucleus Accumbens Associated Protein 2-Neurotrophic Receptor Tyrosine Kinase 2) fusion. Initial workup of our case demonstrated homozygous CDKN2A deletion, but immunohistochemistry for other driver mutations, including IDH1 R132H, BRAF V600E, and H3F3A K27M were negative, and ATRX was retained. Tissue was subsequently submitted for personalized oncogenomic analysis, including whole genome and whole transcriptome sequencing, which demonstrated an activating NTRK2 fusion, as well as high PD-L1 expression, which was subsequently confirmed by immunohistochemistry. Furthermore, H3 and IDH demonstrated wildtype status. These findings suggested the possibility of treatment with either NTRK- or immune checkpoint- inhibitors through active clinical trials. Ultimately, the family pursued standard treatment that involved Head Start III chemotherapy and proton radiotherapy. Notably, at most recent follow upapproximately two years from initial diagnosis, the patient is in disease remission and thriving, suggesting favorable biology despite histologic malignancy. This case illustrates the value of personalized oncogenomics, as the molecular profiling revealed two actionable changes that would not have been apparent through routine diagnostics. NTRK fusions are known oncogenic drivers in a range of cancer types, but this is the first report of a NACC2-NTRK2 fusion in a glioblastoma.

Low-mass stars form from the gravitational collapse of dense molecular cloud cores. While a general consensus picture of this collapse process has emerged, many details on how mass is transferred from cores to stars remain poorly understood. MASSES (Mass Assembly of Stellar Systems and their Evolution with the SMA), an SMA large project, has just finished surveying all 74 Class 0 and Class I protostars in the nearby Perseus molecular cloud to reveal the interplay between fragmentation, angular momentum, and outflows in regulating accretion and setting the final masses of stars. Scientific highlights are presented in this proceedings, covering the topics of episodic accretion, hierarchical thermal Jeans fragmentation, angular momentum transfer, envelope grain sizes, and disk evolution.

The chemistry of smectites from some bentonite deposits derived from intermediate rocks has been examined by electron microprobe methods. A large variation in chemical composition within very short distances, principally controlled by a well-defined negative relationship between Si and A1, and between A1VI and Fe 3+ and A1VI and Mg has been observed. On the other hand, Mg does not vary systematically with either Si or Fe3+. In several bentonites beidellite coexists with montmorillonite and there is a compositional transition between the two smectite minerals, implying the existence of a possible solid-solution series. This transition occurs only when Cheto-type montmorillonites are present, being absent for Wyoming-type montmorillonites. No compositional transition between Wyoming-and Cheto-type montmorillonite was observed. It is believed that the compositional variations reflect initial chemical gradients originated during the devitrification of the volcanic glass, due to the migration of chemical components.

The smectites present in some bentonites from the Island of Milos, Greece, derived from acidic rocks, have been examined by XRD and electron microprobe. The possible influence of loss of alkalis during analysis and contamination by fine grained Si-phases on microanalyses has also been evaluated. Smectites are closely associated with opal-CT and their composition ranges from beidellite to Tatatilla-type montmorillonite. Their chemistry is dominated by negative relationships between Mg and AlVI and Si and total Al. However, it cannot be resolved whether there is a solid-solution between the smectites or whether the variation observed is due to mechanical mixing of domains with different composition.The role of Fe is of minor importance reflecting an inherited factor imposed by the parent rock, but the role of the fluid phase is also important. Beidellite occurs in the rims, while Tatatilla-type montmorillonite, often associated with free opal-CT, is formed in the interior of the altered shards, indicating a variable degree of Si release during glass dissolution. The formation of beidellite is not necessarily associated with Mg uptake.

The Kapalagulu intrusion displays the following sequence of cumulus phase layering in a stratigraphic sequence of 1400 m: Basal Zone (BZ) olivine ± chromite → Intermediate Zone (IZ) olivine + plag + opx →, olivine + plag + opx + cpx → Main Zone (MZ) plag + opx + cpx → plag + cpx + Fe/Ti oxide + apatite. The corresponding cryptic variation is olivine Fo83 − 77 (limited to BZ and IZ), orthopyroxene En82 − 56, clinopyroxene Ca46Mg45Fe9 to Ca43Mg37Fe21 and plagioclase An88 − 80. Reversals of the cryptic variation occur at the base of MZ (minor reversal) and in the middle of MZ (major reversal), and are attributed to the influx of relatively primitive magma. The major reversal indicates that progressive mixing of fresh and residual magmas occurred. Because of the major reversal, inverted pigeonite appears twice in the layered sequence, but at different compositions (En65 and En56). Unlike the cumulus olivine and pyroxene, cumulus plagioclase exhibits a wide range of composition (5−10% An) in individual rocks and even in single crystals.

Electron-microprobe analyses of cumulus olivine, chromite, pyroxene, and plagioclase from layered peridotites and allivalites of the Eastern and Western Layered Series of Rhum demonstrate the presence of cryptic variation. Olivine varies from Fo88-78 within individual units, and there are corresponding changes in the Mg/(Mg+Fe2+) ratios in the pyroxenes and chromites. Plagioclase changes are not so dramatic, but the An-content broadly follows the Mg/(Mg+Fe2+) ratio in the other minerals. The most Fe-(and Na-) rich phases do not occur at the top of lithological units, but some way below. The composition trend above them is reversed. The data are interpreted as the result of periodic infilling of a magma chamber, the new magma mixing with the remains of the previous pulse. Each pulse was followed by a period when fractional crystallization produced the layered rocks. New data on Ni in the olivines suggests that the ratio of the volume of initial magma to volume of layered rocks was about four to one, the initial magma being allied to the high-calcium low-alkali tholeiitic basalts of Skye.

SVcPACNS is a rare inflammatory/immune disorder that typically affects the small blood vessels of the brain. SVcPACNS differs from most adult forms of PACNS by being predominantly lymphocytic, non-granulomatous and non-necrotizing. Previously healthy children are typically affected by range of signs and symptoms, including: seizures, headache, cognitive decline, behavior/personality change, focal neurological deficits and potentially a decreased level of consciousness. Treatment protocols featuring induction (steroids and cyclophosphamide) and subsequent maintenance phases (e.g., mycophenolate mofetil) have been demonstrated to yield favorable outcomes. Since SVcPACNS is characteristically angiography negative, the diagnostic gold standard is brain biopsy. Interpretation of these biopsies is often challenging given the histologic overlap between SVcPACNS and encephalitis. Distinguishing the foregoing is critical since the treatment of these entities is significantly different.

Herein, a rare autopsy case of SVcPACNS in a 4 year old male is presented. This case provides a unique opportunity to review the Alrawi criteria for the histologic diagnosis of PACNS and establish/refine criteria specific to SVcPACNS. Generally, such criteria should feature: 1) an intramural and lymphocyte predominant infiltrate devoid of multinucleated giant cells; 2) structural vessel alterations lacking fibrinoid necrosis; 3) perivascular pathology supportive of an angiocentric process; 4) the absence of encephalitis; and, 5) the absence of a concurrent systemic or rheumatic illness that could account for the CNS findings.

By contrast to infantile spinal muscular atrophy, which usually links to deletions in the SMN genes, fetal onset motor neuron disease is poorly reported. We collected a series of twelve cases of fetal arthrogryposis (16-31 weeks gestational age) with fetal motor neuron disease and excluded infectious diseases, lysosomal storage disease and neuroaxonal dystrophy. Of these twelve, 3 were thought to be ischemic in nature with microvascular alterations and systemic or central nervous system ischemic injury. The remaining 9 all displayed marked reduction in anterior horn motor neurons. Of these 9, four demonstrated mineralised neurons, four demonstrated either neuronal loss or cavitation in the globus pallidus, and in two, degenerating neurons were detectable in the brainstem or globus pallidus. Specific sequencing of SMN1 was performed in 6 of 9 and was reported as normal. Whole exome sequencing was performed in 4 without definitive diagnosis. We conclude that fetal motor neuron disease can be distinguished from ischemic injury, is morphologically heterogeneous, may affect the globus pallidus and is rarely linked to SMN1 mutations.

Northern bobwhite (Colinus virginianus) and scaled quail (Callipepla squamata) have experienced chronic declines within the Rolling Plains ecoregion of Texas. Parasitic infection, which has long been dismissed as a problem in quail, has not been studied thoroughly until recently. A total of 219 northern bobwhite and 101 scaled quail from Mitchell County, Texas were captured and donated from 2014 to 2015, and examined for eyeworm (Oxyspirura petrowi) and caecal worm (Aulonocephalus pennula) infections. In 2014, bobwhites averaged 19.6 ± 1.8 eyeworms and 98.6 ± 8.2 caecal worms, and 23.5 ± 2.1 eyeworms and 129.9 ± 10.7 caecal worms in 2015. Scaled quail averaged 4.8 ± 1.0 eyeworms and 50 ± 6.8 caecal worms in 2014, and 5.7 ± 1.3 eyeworms and 38.1 ± 7.1 caecal worms in 2015. This study expands the knowledge of parasitic infection in quail inhabiting the Rolling Plains of Texas. A significant difference was documented in O. petrowi infection between species but there was no significant difference in A. pennula between quail species. No significant difference was detected in parasite infection between the sexes of both northern bobwhite and scaled quail. This study also documented the highest reported O. petrowi infection in both species of quail. Additional research is needed on the life history and infection dynamics of O. petrowi and A. pennula infections to determine if there are individual- and/or population-level implications due to parasitic infection.

Cerebral hyaline astrocytic inclusions (HAI) have been observed in a subset of patients with epilepsy, structural brain anomalies, and developmental delay. We present a case of a 2.5-year-old male with epilepsy and global developmental delay. Chromosomal microarray detected a copy loss at 22q13 that resulted in a partial deletion of SHANK3 gene. The EEGs revealed seizure activity arising from left frontal central region. Invasive video electrocorticography captured clusters of epileptic spasms, all originating from left antero-lateral frontal lobe rostral to the motor cortex. We utilized routine histology to identify the inclusions and mapped their distribution in the resected portion of the cortex against electrocorticographic data. Histologic analysis revealed the presence of HAI in the posterio-medial portion of the resected cortex, which corresponded to the site of seizure generalization. HAI were present at the resection margin. Immunohistochemistry was largely non-contributory. HAI is a rare but emerging entity that is associated with epilepsy. To our knowledge, the distribution of inclusions in HAI has never been mapped to electrophysiologic data. In our case, seizure generalization correlated with the inclusions distribution. This suggests that the inclusions may: 1) play a role in epileptogenesis; or, 2) be a biomarker of disease distribution. Finally, the presence of the HAI at the resection margin may foreshadow future seizure activity in this patient.

The aim of the present experiment was to examine the influence of feeding diets containing a probiotic containing three Bacillus subtilis strains or zinc bacitracin (BMD) on bird performance, intestinal mucosa-associated avian pathogenic Escherichia coli (APEC), intestinal morphology and litter water-soluble phosphorus (WSP) of broilers fed corn-based diets. Three treatments were employed, either a control diet; the control diet supplemented with probiotic at 7.5 × 104 colony forming units (cfu) /g of feed or the supplemented with BMD (50g/tonne feed). Broiler starter and finisher diets, based on corn and soybean meal, were formulated and fed ad libitum to seven pens of 50 male broilers per treatment from days 1 to 42. During the 1-35 d periods, feed intake and weight gain were not influenced (P > 0.05) by dietary treatments, but probiotic supplementation improved (P < 0.05) 35-d FCR compared to the control and BMD-supplemented diets (1.395, 1.447 and 1.484, respectively). During the 1-42d period, feed intake and weight gain were not influenced (P > 0.05) by dietary treatments. However, probiotic improved (P = 0.05) and BMD tended (P = 0.07) to improve FCR compared to control diet. Villus height and crypt depth in the duodenum and jejunum were not influenced (P > 0.05) by dietary treatment. The number of mucosa-associated APEC was not influenced (P > 0.05) by dietary treatments. Probiotic and BMD supplementation had no effect (P > 0.05) on litter total phosphorus. However, BMD reduced (P < 0.05) litter WSP compared to control and probiotic supplemented diet. In conclusion, probiotic supplementation had no effect on intestinal morphology or WSP but improved broiler performance and can be used as an alternative to antibiotic growth promoters.

The Northumbrian Fault-block, forming the central part of the Pennine Chain, is a region of gently tilted Carboniferous sediments, bounded on the north, west, and south by major faultlines. It is divided naturally into two structurally complementary areas, symmetrically disposed to the north and south of the syncline of Stainmore. The present paper is concerned exclusively with the northern area, named by F. M. Trotter and S. E. Hollingworth the “Alston Block” (1928) and by H. G. A. Hickling the “Cross Fell Block” (1930). The first-named authors, who have recently completed a revision of the Geological Survey sheet covering the north-west corner of the block, have discussed in detail the structure of that district and have described the broad outlines of the tectonic history of the block (1928, 1932).