1865-04-27 George Palmer inquires about the welfare of Patrick Lang, whose sister is a servant in Palmer\u27s home

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Intellectual disability, unusual facial morphology and hand anomalies in sibs

Here we report on a Portuguese family with three sisters who shared moderate intellectual disability, unusual facial morphology (short palpebral fissures; broad nasal tip; thin upper and lower vermillion; broad and pointed chin) and hand anomalies in two of them (short left third and fifth right metacarpals in one case; marked syndactyly between the third and fourth fingers in another). One of the sisters had microcephaly and short stature, and the other two were obese. Obesity and somewhat similar facial features were also present in the otherwise healthy mother. Despite the overlap with several known syndromes (Albright osteodystrophy; Filippi syndrome; Rubinstein-Taybi syndrome; microdeletion 2q37), we suggest this condition is previously unreported, and most likely displays an autosomal recessive pattern of inheritance

Reach-scale bankfull channel types can exist independently of catchment hydrology

© 2020 John Wiley & Sons, Ltd. Reach-scale morphological channel classifications are underpinned by the theory that each channel type is related to an assemblage of reach- and catchment-scale hydrologic, topographic, and sediment supply drivers. However, the relative importance of each driver on reach morphology is unclear, as is the possibility that different driver assemblages yield the same reach morphology. Reach-scale classifications have never needed to be predicated on hydrology, yet hydrology controls discharge and thus sediment transport capacity. The scientific question is: do two or more regions with quantifiable differences in hydrologic setting end up with different reach-scale channel types, or do channel types transcend hydrologic setting because hydrologic setting is not a dominant control at the reach scale? This study answered this question by isolating hydrologic metrics as potential dominant controls of channel type. Three steps were applied in a large test basin with diverse hydrologic settings (Sacramento River, California) to: (1) create a reach-scale channel classification based on local site surveys, (2) categorize sites by flood magnitude, dimensionless flood magnitude, and annual hydrologic regime type, and (3) statistically analyze two hydrogeomorphic linkages. Statistical tests assessed the spatial distribution of channel types and the dependence of channel type morphological attributes by hydrologic setting. Results yielded 10 channel types. Nearly all types existed across all hydrologic settings, which is perhaps a surprising development for hydrogeomorphology. Downstream hydraulic geometry relationships were statistically significant. In addition, cobble-dominated uniform streams showed a consistent inverse relationship between slope and dimensionless flood magnitude, an indication of dynamic equilibrium between transport capacity and sediment supply. However, most morphological attributes showed no sorting by hydrologic setting. This study suggests that median hydraulic geometry relations persist across basins and within channel types, but hydrologic influence on geomorphic variability is likely due to local influences rather than catchment-scale drivers. © 2020 John Wiley & Sons, Ltd

Regularity for harmonic maps into certain Pseudo-Riemannian manifolds

In this article, we investigate the regularity for certain elliptic systems without a $L^2$-antisymmetric structure. As applications, we prove some $\epsilon$-regularity theorems for weakly harmonic maps from the unit ball $B= B(m) \subset \mathbb{R}^m$ $(m\geq2)$ into certain pseudo-Riemannian manifolds: standard stationary Lorentzian manifolds, pseudospheres $\mathbb{S}^n_\nu \subset \mathbb{R}^{n+1}_\nu$ $(1\leq\nu \leq n)$ and pseudohyperbolic spaces $\mathbb{H}^n_\nu \subset \mathbb{R}^{n+1}_{\nu+1}$ $(0\leq\nu \leq n-1)$. Consequently, such maps are shown to be H\"{o}lder continuous (and as smooth as the regularity of the targets permits) in dimension $m=2$. In particular, we prove that any weakly harmonic map from a disc into the De-Sitter space $\mathbb{S}^n_1$ or the Anti-de-Sitter space $\mathbb{H}^n_1$ is smooth. Also, we give an alternative proof of the H\"{o}lder continuity of any weakly harmonic map from a disc into the Hyperbolic space $\mathbb{H}^n$ without using the fact that the target is nonpositively curved. Moreover, we extend the notion of generalized (weakly) harmonic maps from a disc into the standard sphere $\mathbb{S}^n$ to the case that the target is $\mathbb{S}^n_\nu$ $(1\leq\nu \leq n)$ or $\mathbb{H}^n_\nu$ $(0\leq\nu \leq n-1)$, and obtain some $\epsilon$-regularity results for such generalized (weakly) harmonic maps.Comment: to appear in J. Math. Pures App

Electronic voting to encourage interactive lectures: a randomised trial

Background: Electronic Voting Systems have been used for education in a variety of disciplines. Outcomes from these studies have been mixed. Because results from these studies have been mixed, we examined whether an EVS system could enhance a lecture's effect on educational outcomes. Methods: A cohort of 127 Year 5 medical students at the University of Adelaide was stratified by gender, residency status and academic record then randomised into 2 groups of 64 and 63 students. Each group received consecutive 40-minute lectures on two clinical topics. One group received the EVS for both topics. The other group received traditional teaching only. Evaluation was undertaken with two, 15-question multiple-choice questionnaires (MCQ) assessing knowledge and problem solving and undertaken as a written paper immediately before and after the lectures and repeated online 8–12 weeks later. Standardised institutional student questionnaires were completed for each lecture and independent observers assessed student behaviour during the lectures. Lecturer's opinions were assessed by a questionnaire developed for this study. Results: Two-thirds of students randomised to EVS and 59% of students randomised to traditional lectures attended. One-half of the students in the EVS group and 41% in the traditional group completed all questionnaires. There was no difference in MCQ scores between EVS and traditional lectures (p = 0.785). The cervical cancer lectures showed higher student ranking in favour of EVS in all parameters. The breast cancer lectures showed higher ranking in favour of traditional lectures in 5 of 7 parameters (p < 0.001). The observed higher-order lecturer-students interactions were increased in the EVS lecture for one lecturer and reduced for the other. Both lecturers felt that the EVS lectures were difficult to prepare, that they were able to keep to time in the traditional lectures, that the educational value of both lecture styles was similar, and that they were neutral-to-slightly favourably disposed to continue with the EVS technology. The 2 lecturers disagreed regarding the ease of preparation of the traditional lecture, their ability to keep to time in the EVS lecture, and personal satisfaction with the EVS lecture. The lecturers felt that EVS encouraged student participation and helped identify where students were having difficulty. Conclusion: In this setting, EVS technology used in large group lectures did not offer significant advantages over the more traditional lecture format.Paul M Duggan, Edward Palmer and Peter Devit

Zika virus impairs the development of blood vessels in a mouse model of congenital infection

Zika virus (ZIKV) is associated with brain development abnormalities such as primary microcephaly, a severe reduction in brain growth. Here we demonstrated in vivo the impact of congenital ZIKV infection in blood vessel development, a crucial step in organogenesis. ZIKV was injected intravenously in the pregnant type 2 interferon (IFN)-deficient mouse at embryonic day (E) 12.5. The embryos were collected at E15.5 and postnatal day (P)2. Immunohistochemistry for cortical progenitors and neuronal markers at E15.5 showed the reduction of both populations as a result of ZIKV infection. Using confocal 3D imaging, we found that ZIKV infected brain sections displayed a reduction in the vasculature density and vessel branching compared to mocks at E15.5; altogether, cortical vessels presented a comparatively immature pattern in the infected tissue. These impaired vascular patterns were also apparent in the placenta and retina. Moreover, proteomic analysis has shown that angiogenesis proteins are deregulated in the infected brains compared to controls. At P2, the cortical size and brain weight were reduced in comparison to mock-infected animals. In sum, our results indicate that ZIKV impairs angiogenesis in addition to neurogenesis during development. The vasculature defects represent a limitation for general brain growth but also could regulate neurogenesis directly

Gammaretrovirus-mediated correction of SCID-X1 is associated with skewed vector integration site distribution in vivo

We treated 10 children with X-linked SCID (SCID-X1) using gammaretrovirus-mediated gene transfer. Those with sufficient follow-up were found to have recovered substantial immunity in the absence of any serious adverse events up to 5 years after treatment. To determine the influence of vector integration on lymphoid reconstitution, we compared retroviral integration sites (RISs) from peripheral blood CD3(+) T lymphocytes of 5 patients taken between 9 and 30 months after transplantation with transduced CD34(+) progenitor cells derived from 1 further patient and I healthy donor. Integration occurred preferentially in gene regions on either side of transcription start sites, was clustered, and correlated with the expression level in CD34(+) progenitors during transduction. In contrast to those in CD34(+) cells, RISs recovered from engrafted CD3(+)T cells were significantly overrepresented within or near genes encoding proteins with kinase or transferase activity or involved in phosphorus metabolism. Although gross patterns of gene expression were unchanged in transduced cells, the divergence of RIS target frequency between transduced progenitor cells and post-thymic T lymphocytes indicates that vector integration influences cell survival, engraftment, or proliferation

Clinical-pathological study on β-APP, IL-1β, GFAP, NFL, Spectrin II, 8OHdG, TUNEL, miR-21, miR-16, miR-92 expressions to verify DAI-diagnosis, grade and prognosis

Traumatic brain injury (TBI) is one of the most important death and disability cause, involving substantial costs, also in economic terms, when considering the young age of the involved subject. Aim of this paper is to report a series of patients treated at our institutions, to verify neurological results at six months or survival; in fatal cases we searched for βAPP, GFAP, IL-1β, NFL, Spectrin II, TUNEL and miR-21, miR-16, and miR-92 expressions in brain samples, to verify DAI diagnosis and grade as strong predictor of survival and inflammatory response. Concentrations of 8OHdG as measurement of oxidative stress was performed. Immunoreaction of β-APP, IL-1β, GFAP, NFL, Spectrin II and 8OHdG were significantly increased in the TBI group with respect to control group subjects. Cell apoptosis, measured by TUNEL assay, were significantly higher in the study group than control cases. Results indicated that miR-21, miR-92 and miR-16 have a high predictive power in discriminating trauma brain cases from controls and could represent promising biomarkers as strong predictor of survival, and for the diagnosis of postmortem traumatic brain injury

Multiple congenital melanocytic nevi and neurocutaneous melanosis are caused by postzygotic mutations in codon 61 of NRAS

Congenital melanocytic nevi (CMN) can be associated with neurological abnormalities and an increased risk of melanoma. Mutations in NRAS, BRAF, and Tp53 have been described in individual CMN samples; however, their role in the pathogenesis of multiple CMN within the same subject and development of associated features has not been clear. We hypothesized that a single postzygotic mutation in NRAS could be responsible for multiple CMN in the same individual, as well as for melanocytic and nonmelanocytic central nervous system (CNS) lesions. From 15 patients, 55 samples with multiple CMN were sequenced after site-directed mutagenesis and enzymatic digestion of the wild-type allele. Oncogenic missense mutations in codon 61 of NRAS were found in affected neurological and cutaneous tissues of 12 out of 15 patients, but were absent from unaffected tissues and blood, consistent with NRAS mutation mosaicism. In 10 patients, the mutation was consistently c.181C>A, p.Q61K, and in 2 patients c.182A>G, p.Q61R. All 11 non-melanocytic and melanocytic CNS samples from 5 patients were mutation positive, despite NRAS rarely being reported as mutated in CNS tumors. Loss of heterozygosity was associated with the onset of melanoma in two cases, implying a multistep progression to malignancy. These results suggest that single postzygotic NRAS mutations are responsible for multiple CMN and associated neurological lesions in the majority of cases

Phenotypic and molecular assessment of seven patients with 6p25 deletion syndrome: Relevance to ocular dysgenesis and hearing impairment

BACKGROUND: Thirty-nine patients have been described with deletions involving chromosome 6p25. However, relatively few of these deletions have had molecular characterization. Common phenotypes of 6p25 deletion syndrome patients include hydrocephalus, hearing loss, and ocular, craniofacial, skeletal, cardiac, and renal malformations. Molecular characterization of deletions can identify genes that are responsible for these phenotypes. METHODS: We report the clinical phenotype of seven patients with terminal deletions of chromosome 6p25 and compare them to previously reported patients. Molecular characterization of the deletions was performed using polymorphic marker analysis to determine the extents of the deletions in these seven 6p25 deletion syndrome patients. RESULTS: Our results, and previous data, show that ocular dysgenesis and hearing impairment are the two most highly penetrant phenotypes of the 6p25 deletion syndrome. While deletion of the forkhead box C1 gene (FOXC1) probably underlies the ocular dysgenesis, no gene in this region is known to be involved in hearing impairment. CONCLUSIONS: Ocular dysgenesis and hearing impairment are the two most common phenotypes of 6p25 deletion syndrome. We conclude that a locus for dominant hearing loss is present at 6p25 and that this locus is restricted to a region distal to D6S1617. Molecular characterization of more 6p25 deletion patients will aid in refinement of this locus and the identification of a gene involved in dominant hearing loss