Optimal treatment of social phobia: systematic review and meta-analysis

This article proposes a number of recommendations for the treatment of generalized social phobia, based on a systematic literature review and meta-analysis. An optimal treatment regimen would include a combination of medication and psychotherapy, along with an assertive clinical management program. For medications, selective serotonin reuptake inhibitors and dual serotonin-norepinephrine reuptake inhibitors are first-line choices based on their efficacy and tolerability profiles. The nonselective monoamine oxidase inhibitor, phenelzine, may be more potent than these two drug classes, but because of its food and drug interaction liabilities, its use should be restricted to patients not responding to selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors. There are other medication classes with demonstrated efficacy in social phobia (benzodiazepines, antipsychotics, alpha-2-delta ligands), but due to limited published clinical trial data and the potential for dependence and withdrawal issues with benzodiazepines, it is unclear how best to incorporate these drugs into treatment regimens. There are very few clinical trials on the use of combined medications. Cognitive behavior therapy appears to be more effective than other evidence-based psychological techniques, and its effects appear to be more enduring than those of pharmacotherapy. There is some evidence, albeit limited to certain drug classes, that the combination of medication and cognitive behavior therapy may be more effective than either strategy used alone. Generalized social phobia is a chronic disorder, and many patients will require long-term support and treatment

A mitotic kinase scaffold depleted in testicular seminomas impacts spindle orientation in germ line stem cells.

Correct orientation of the mitotic spindle in stem cells underlies organogenesis. Spindle abnormalities correlate with cancer progression in germ line-derived tumors. We discover a macromolecular complex between the scaffolding protein Gravin/AKAP12 and the mitotic kinases, Aurora A and Plk1, that is down regulated in human seminoma. Depletion of Gravin correlates with an increased mitotic index and disorganization of seminiferous tubules. Biochemical, super-resolution imaging, and enzymology approaches establish that this Gravin scaffold accumulates at the mother spindle pole during metaphase. Manipulating elements of the Gravin-Aurora A-Plk1 axis prompts mitotic delay and prevents appropriate assembly of astral microtubules to promote spindle misorientation. These pathological responses are conserved in seminiferous tubules from Gravin(-/-) mice where an overabundance of Oct3/4 positive germ line stem cells displays randomized orientation of mitotic spindles. Thus, we propose that Gravin-mediated recruitment of Aurora A and Plk1 to the mother (oldest) spindle pole contributes to the fidelity of symmetric cell division

Engineering the interface between cellular chassis and synthetic biological systems

Thesis (Ph. D.)--Massachusetts Institute of Technology, Biological Engineering Division, 2008.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Includes bibliographical references (p. 165-176).The aim of my thesis is to help enable the engineering of biological systems that behave in a predictable manner. Well-established techniques exist to engineer systems that behave as expected. Here, I apply such techniques to two aspects of the engineering of biological systems. First, I address the design and construction of standard biological devices in a manner that facilitates reuse in higher-order systems. I describe the design and construction of an exemplar device, an engineered cell-cell communication receiver using standard biological parts (refined genetic objects designed to support physical and functional composition). I adopt a conventional framework for describing the behavior of engineered devices and use the adopted framework to design and interpret experiments that describe the behavior of the receiver. The output of the device is the activity of a promoter reported in units of Polymerases Per Second (PoPS), a common signal carrier. Second, I begin to address the coupling that exists between engineered biological systems and the host cell, or chassis. I propose that the coupling between engineered biological systems and the cellular chassis might be reduced if fewer resources were shared between the system and the chassis. I describe the construction of cellular chassis expressing both T7 RNA polymerases (RNAP) and orthogonal ribosomes that are unused by the chassis but are available for use by an engineered system. I implement a network in which the orthogonal ribosomal RNA and the gene encoding T7 RNAP are transcribed by T7 RNAP. In turn, the orthogonal ribosomes translate the T7 RNAP message. In addition, the T7 RNAP and orthogonal ribosomes express a repressor that inhibits transcription of both the T7 RNAP and orthogonal ribosomes.(cont.) As a result, the orthogonal RNAP and ribosomes are auto-generating and self-regulating. The provision of resources unused by the cellular chassis and dedicated to an engineered biological system forms the beginnings of a biological virtual machine.by Bartholomew Canton.Ph.D

Reconstruction of the time-dependent electronic wave packet arising from molecular autoionization

Autoionizing resonances are paradigmatic examples of two-path wave interferences between direct photoionization, which takes a few attoseconds, and ionization via quasi-bound states, which takes much longer. Time-resolving the evolution of these interferences has been a long-standing goal, achieved recently in the helium atom owing to progress in attosecond technologies. However, already for the hydrogen molecule, similar time imaging has remained beyond reach due to the complex interplay between fast nuclear and electronic motions. We show how vibrationally resolved photoelectron spectra of H2 allow one to reconstruct the associated subfemtosecond autoionization dynamics by using the ultrafast nuclear dynamics as an internal clock, thus forgoing ultrashort pulses. Our procedure should be general for autoionization dynamics in molecules containing light nuclei, which are ubiquitous in chemistry and biologyThis work was supported by European Research Council advanced grant 290853-XCHEM within the seventh framework program of the European Union. We also acknowledge the financial support from MINECO projects FIS2013-42002-R and FIS2016-77889-R, and the European COST (Cooperation in Science and Technology) Action XLIC CM1204, and the computer time from the Centro de Computación Científica de la Universidad Autónoma de Madrid and Marenostrum Supercomputer Center. A.P. acknowledges a Ramón y Cajal contract from the Ministerio de Economía y Competitividad (Spain). F.M. acknowledges support from the “Severo Ochoa” Programme for Centres of Excellence in R&D (MINECO, grant SEV-2016-0686) and the “María de Maeztu” Programme for Units of Excellence in R&D (MDM-2014-0377). S.E.C. acknowledges funding from the Helmoltz Recognition Award. The Extreme Light Infrastructure Attosecond Light Pulse Source project (GINOP-2.3.6-15-2015-00001) was financed by the European Union and cofinanced by the European Regional Development Fun

Book Reviews

Reviews of the following books: Greater Portland Celebration 350: A Commemorative Edition, edited by Albert F. Barnes; Portsmouth-Built: Submarines of the Portsmouth Naval Shipyard by Richard E. Winslow, III; A Glimpse of Sion’s Glory: Puritan Radicalism in New England, 1620-1660 by Philip R. Gura; The Socialist Alternative: Utopian Experiments and the Socialist Party of Maine, 1895-1914 by Charles Scontras; Restitution: The Land Claims of the Mashpee, Passamaquoddy, and Penobscot Indians of New England by Paul Brodeur

Reconstruction of the time-dependent electronic wave packet arising from molecular autoionization

The time evolution of an electronic molecular wave packet is determined using nuclear motion as an internal clock of the system

Reconstruction of the superior vena cava: Benefits of postoperative surveillance and secondary endovascular interventions

AbstractPurpose: Superior vena cava (SVC) reconstructions are rarely performed; therefore the need for surveillance and the results of secondary interventions are unknown. Methods: During a 14-year period 19 patients (11 male, 8 female; mean age 41.9 years, range 8 to 69 years) underwent SVC reconstruction for symptomatic nonmalignant disease. Causes included mediastinal fibrosis (n = 12), indwelling foreign bodies (n = 4), idiopathic thrombosis (n = 2), and antithrombin III deficiency (n = 1). Spiral saphenous vein graft (n = 14), polytetrafluoroethylene (n = 4), or human allograft (n = 1) was implanted. Results: No early death or pulmonary embolism occurred. Four early graft stenoses or thromboses (spiral saphenous vein graft, n = 2, polytetrafluoroethylene, n = 2) required thrombectomy, with success in three. During a mean follow-up of 49.5 months (range, 4.7 to 137 months), 95 imaging studies were performed (average, five per patient; range, one to 10 studies). Venography detected mild or moderate graft stenosis in seven patients; two progressed to severe stenosis. Two additional grafts developed early into severe stenosis. Four of 19 grafts occluded during follow-up (two polytetrafluoroethylene, two spiral saphenous vein graft). Computed tomography failed to identify stenosis in two grafts, magnetic resonance imaging failed to confirm one stenosis and one graft occlusion, and duplex scanning was inconclusive on graft patency in 10 patients. Angioplasty was performed in all four patients with severe stenosis, with simultaneous placement of Wallstents in two. One of the Wallstents occluded at 9 months. Repeat percutaneous transluminal angioplasty was necessary in two patients, with placement of Palmaz stents in one. Only one graft occlusion and one severe graft stenosis occurred beyond 1 year. The primary, primary-assisted, and secondary patency rates were 61%, 78%, and 83% at 1 year and 53%, 70%, and 74% at 5 years, respectively. Conclusions: Long-term secondary patency rates justify SVC grafting for benign disease. Postoperative surveillance with contrast venography is indicated in the first year to detect graft problems. Endovascular techniques may salvage and improve the patency of SVC grafts. (J Vasc Surg 1998;27:287-301.

Gravitational waves: search results, data analysis and parameter estimation

The Amaldi 10 Parallel Session C2 on gravitational wave (GW) search results, data analysis and parameter estimation included three lively sessions of lectures by 13 presenters, and 34 posters. The talks and posters covered a huge range of material, including results and analysis techniques for ground-based GW detectors, targeting anticipated signals from different astrophysical sources: compact binary inspiral, merger and ringdown; GW bursts from intermediate mass binary black hole mergers, cosmic string cusps, core-collapse supernovae, and other unmodeled sources; continuous waves from spinning neutron stars; and a stochastic GW background. There was considerable emphasis on Bayesian techniques for estimating the parameters of coalescing compact binary systems from the gravitational waveforms extracted from the data from the advanced detector network. This included methods to distinguish deviations of the signals from what is expected in the context of General Relativity