New Hampshire Constitutional Convention

New Hampshire\u27s tenth constitutional convention, upon whose labors the voters will pass judgment in November, 1920, offers a striking contrast to most constitutional conventions of recent years.\u27 It met originally in June, 1918, sat for three days, during which it organized, appointed its committees, debated andt disposed of an important constitutional question, and then adjourned awaiting the quieter days of peace. Upon reconvening in January, igo, it concluded its work within seventeen days, at an expense of less than $5oooo, and proposed only seven amendments, five of which had been submitted to the voters by previous conventions. For a body of over four hundred men, meeting in the midst of rapidly changing conditions and dealing with a constitution which is today substantially the same document as that adopted in 1784, this may well be said to be an unusual record of brevity and despatch

Book Reviews

What does a judge do when he decides a case? It would be interesting to collect the answers ranging from those furnished by primitive systems of law in which the judge was supposed to consult the gods to the ultra-modern, rather profane system described to me recently by a retrospective judge: I make up my mind which way the case ought to be decided, and then I see if I can\u27t get some legal ground to make it stick. Perhaps the widespread impression is the curiously erroneous one lampooned by Gnaeus Flavius (Kantorowitz). The judge is supposed to sit at a green baize tablethe German equivalent in suggestion for our red tape-with nothing before him but a copy of the Biirgerliches Gesetzbucl. Personally, he has no equipment but a perfect thinking machine. The facts are presented to him and a mechanically perfect conclusion is automatically reached. Disregarding entirely the unattainability of this ideal degree of the elimination of the personal equation, one may well ask whether the ideal itself is worth striving to approximate

Hematopoietic Defects in rps29 Mutant Zebrafish Depend Upon p53 Activation

Disruption of ribosomal proteins is associated with hematopoietic phenotypes in cell culture and animal models. Mutations in ribosomal proteins are seen in patients with Diamond Black- fan anemia, a rare congenital disease characterized by red cell aplasia and distinctive cranio- facial anomalies. A zebrafish screen uncovered decreased hematopoietic stem cells in embryos with mutations in ribosomal protein rps29. Here, we determined that rps29L/L embryos also have red blood cell defects and increased apoptosis in the head. As the p53 pathway has been shown to play a role in other ribosomal protein mutants, we studied the genetic relationship of rps29 and p53. Transcriptional profiling revealed that genes upregulated in the rps29 mutant are enriched for genes upregulated by p53 after irradiation. p53 mutation near completely rescues the rps29 morphological and hematopoietic phenotypes, demonstrating that p53 medi- ates the effects of rps29 knockdown. We also identified neuronal gene orthopedia protein a (otpa) as one whose expression correlates with rps29 expression, suggesting that levels of expression of some genes are dependent on rps29 levels. Together, our studies demonstrate a role of p53 in mediating the cellular defects associated with rps29 and establish a role for rps29 and p53 in hematopoietic stem cells and red blood cell development.Stem Cell and Regenerative Biolog

Book Reviews

Although the three lectures contained in this volume are propounded as a trinity, the reader will not find in them that unity which is of the essence of a trinity, as distinguished from an aggregate of three. The author proposes a triune division of legal science, Past, Present and Future. But the first lecture deals with a particular phase of the past, the second with a remotely related phase of the present, and the last with a quite unrelated phase of the future, so that they have little in common, save the brilliance that sparkles through them all

A pilot study of performance among hospitalised elderly patients on a novel test of visuospatial cognition: the letter and shape drawing (LSD) test.

peer-reviewedObjectives. Conventional bedside tests of visuospatial function such as the clock drawing (CDT) and intersecting pentagons tests (IPT) are subject to considerable inconsistency in their delivery and interpretation. We compared performance on a novel test – the letter and shape drawing (LSD) test –with these conventional tests in hospitalised elderly patients. Methods. The LSD, IPT, CDT and the Montreal Cognitive Assessment (MoCA) were performed in 40 acute elderly medical inpatients at University Hospital Limerick The correlation between these tests was examined as well as the accuracy of the visuospatial tests to identify significant cognitive impairment on the MoCA. Results. The patients (mean age 81.0±7.71; 21 female) had a median MoCA score of 15.5 (range = 1–29). There was a strong, positive correlation between the LSD and both the CDT (r = 0.56) and IPT (r = 0.71). The correlation between the LSD and MoCA (r = 0.91) was greater than for the CDT and IPT (both 0.67). The LSD correlated highly with all MoCA domains (ranging from 0.54 to 0.86) and especially for the domains of orientation (r = 0.86), attention (0.81) and visuospatial function (r = 0.73). Two or more errors on the LSD identified 90% (26/29) of those patients with MoCA scores of ⩽20, which was substantially higher than for the CDT (59%) and IPT (55%). Conclusion. The LSD is a novel test of visuospatial function that is brief, readily administered and easily interpreted. Performance correlates strongly with other tests of visuospatial ability, with favourable ability to identify patients with significant impairment of general cognition.PUBLISHEDpeer-reviewe

Human Papillomavirus E6 Triggers Upregulation of the Antiviral and Cancer Genomic DNA Deaminase APOBEC3B

ABSTRACT Several recent studies have converged upon the innate immune DNA cytosine deaminase APOBEC3B (A3B) as a significant source of genomic uracil lesions and mutagenesis in multiple human cancers, including those of the breast, head/neck, cervix, bladder, lung, ovary, and other tissues. A3B is upregulated in these tumor types relative to normal tissues, but the mechanism is unclear. Because A3B also has antiviral activity in multiple systems and is a member of the broader innate immune response, we tested the hypothesis that human papillomavirus (HPV) infection causes A3B upregulation. We found that A3B mRNA expression and enzymatic activity were upregulated following transfection of a high-risk HPV genome and that this effect was abrogated by inactivation of E6. Transduction experiments showed that the E6 oncoprotein alone was sufficient to cause A3B upregulation, and a panel of high-risk E6 proteins triggered higher A3B levels than did a panel of low-risk or noncancer E6 proteins. Knockdown experiments in HPV-positive cell lines showed that endogenous E6 is required for A3B upregulation. Analyses of publicly available head/neck cancer data further support this relationship, as A3B levels are higher in HPV-positive cancers than in HPV-negative cancers. Taken together with the established role for high-risk E6 in functional inactivation of TP53 and published positive correlations in breast cancer between A3B upregulation and genetic inactivation of TP53, our studies suggest a model in which high-risk HPV E6, possibly through functional inactivation of TP53, causes derepression of A3B gene transcription. This would lead to a mutator phenotype that explains the observed cytosine mutation biases in HPV-positive head/neck and cervical cancers

The Effect of Travel Burden on Depression and Anxiety in African American Women Living with Systemic Lupus

The United States has a deficit of rheumatology specialists. This leads to an increased burden in accessing care for patients requiring specialized care. Given that most rheumatologists are located in urban centers at large hospitals, many lupus patients must travel long distances for routine appointments. The present work aims to determine whether travel burden is associated with increased levels of depression and anxiety among these patients. Data for this study were collected from baseline visits of patients participating in a lupus study at MUSC. A travel/economic burden survey was assessed as well as the 8-item Patient Health Questionnaire (PHQ-8) and the 7-item Generalized Anxiety Disorder (GAD-7) survey as measures of depression and anxiety, respectively. Linear regression models were used to assess the relationship between travel burden and depression and anxiety. Frequency of healthcare visits was significantly associated with increased depression (β = 1.3, p = 0.02). Significant relationships were identified between anxiety and requiring time off from work for healthcare appointments (β = 4, p = 0.02), and anxiety and perceived difficulty in traveling to primary care providers (β = 3.1, p = 0.04). Results from this study provide evidence that travel burden can have an effect on lupus patients’ anxiety and depression levels

Constraining primordial non-Gaussianity with cosmological weak lensing: shear and flexion

We examine the cosmological constraining power of future large-scale weak lensing surveys on the model of \emph{Euclid}, with particular reference to primordial non-Gaussianity. Our analysis considers several different estimators of the projected matter power spectrum, based on both shear and flexion, for which we review the covariances and Fisher matrices. The bounds provided by cosmic shear alone for the local bispectrum shape, marginalized over $\sigma_8$, are at the level of $\Delta f_\mathrm{NL} \sim 100$. We consider three additional bispectrum shapes, for which the cosmic shear constraints range from $\Delta f_\mathrm{NL}\sim 340$ (equilateral shape) up to $\Delta f_\mathrm{NL}\sim 500$ (orthogonal shape). The competitiveness of cosmic flexion constraints against cosmic shear ones depends on the galaxy intrinsic flexion noise, that is still virtually unconstrained. Adopting the very high value that has been occasionally used in the literature results in the flexion contribution being basically negligible with respect to the shear one, and for realistic configurations the former does not improve significantly the constraining power of the latter. Since the flexion noise decreases with decreasing scale, by extending the analysis up to $\ell_\mathrm{max} = 20,000$ cosmic flexion, while being still subdominant, improves the shear constraints by $\sim 10$ when added. However on such small scales the highly non-linear clustering of matter and the impact of baryonic physics make any error estimation uncertain. By considering lower, and possibly more realistic, values of the flexion intrinsic shape noise results in flexion constraining power being a factor of $\sim 2$ better than that of shear, and the bounds on $\sigma_8$ and $f_\mathrm{NL}$ being improved by a factor of $\sim 3$ upon their combination. (abridged)Comment: 30 pages, 4 figures, 4 tables. To appear on JCA