Dominantly Inherited Amyotrophic Lateral Sclerosis (Motor Neuron Disease)

The term amyotrophic lateral sclerosis was first introduced by Charcot to describe cases with mixed upper and lower motor neuron signs without sensory impairment. Later the syndromes of progressive bulbar palsy (PBP) and progressive muscular atrophy (PMA) were recognized to be variations of the same pathological process, and ALS was used as an inclusive term to refer to these syndromes as well. Although some authors reserve the term ALS for the specific syndrome of mixed upper and lower motor neuron lesions and use the term “motor neuron disease” to refer to the constellation of syndromes, most of the literature on familial cases uses ALS as a generic title. We will adhere to this convention

Does the Meguma Terrane Extend into SW England?

The peri-Gondwanan Meguma terrane of southern Nova Scotia, Canada, is the only major lithotectonic element of the northern Appalachian orogen that has no clear correlatives elsewhere in the Appalachians and lacks firm linkages to the Caledonide and Variscan orogens of western and southern Europe. This characteristic is in contrast with its immediate peri-Gondwanan neighbor, Avalonia, which has features in common with portions of Carolinia in the southern Appalachians and has been traced from the Rhenohercynian Zone of southern Britain eastward around the Bohemian Massif to the Carpathians and western Pontides. At issue is the tendency in Europe to assign all peri-Gondwanan terranes lying outboard of the Rheic suture to Avalonia, characterized by relatively juvenile basement and detrital zircon ages that include Mesoproterozoic populations, and those inboard of the suture to Cadomia, characterized by a more evolved basement and detrital zircon ages that match Paleoproterozoic and older sources in the West African craton.    Although the unexposed basements of Avalonia and Meguma are thought to be isotopically very similar, the Meguma sedimentary cover contains scarce Mesoproterozoic zircon and is dominated instead by Neoproterozoic and Paleoproterozoic populations like those of Cadomia. Hence, felsic magma produced by crustal melting in the Meguma terrane (e.g. the ca. 370 Ma South Mountain Batholith) is isotopically more juvenile (eNd = –5 to –1, TDM = 1.3 Ga) than the rocks it intruded (eNd= –12 to –7, TDM = 1.7 Ga). By contrast, felsic magma produced by crustal melting in Avalonia (eNd = –1 to +6, TDM = 0.7–1.2 Ga) is isotopically similar to its host rocks (eNd = –3 to +4, TDM = 0.9–1.4).    The isotopic relationship shown by the Meguma terrane has also been recognized in the South Portuguese Zone of southern Spain, which is traditionally assigned to Avalonia. However, the Sierra Norte Batholith of the South Portuguese Zone (ca. 330 Ma; eNd = +1 to –3, TDM = 0.9–1.2 Ga) is on average more juvenile than the Late Devonian host rocks (eNd = –5 to –11) it intruded, suggesting instead an extension of the Meguma terrane into Europe. Available data for the Cornubian Batholith of SW England (ca. 275–295 Ma; eNd = –4 to –7, TDM = 1.3–1.8 Ga) and the Devonian–Carboniferous metasedimentary rocks it intruded (eNd = –8 to –11) suggests this may also be true of that part of the southern Britain (Rhenohercynian Zone) with which the South Portuguese Zone is traditionally correlated.SOMMAIRELe terrane péri-gondwanien de Meguma en Nouvelle-Écosse au Canada, est le seul grand élément lithotectonique de l’orogène des Appalaches du Nord qui n’ait pas de correspondant avéré ailleurs dans les Appalaches et qui ne montre aucun lien sûr avec les orogènes calédonienne et varisque de l’ouest et du sud de l’Europe.  Cette situation contraste avec celle de son voisin péri-gondwanien immédiat, l’Avalonie, qui partage certaines caractéristiques avec des portions de Carolinia des Appalaches du sud et qui a été suivi à partir de la zone rhénohercynienne dans le sud de la Grande-Bretagne vers l’est autour du massif bohémien jusqu’aux Carpates et l’ouest de la chaîne pontique.  Ce qui est en question ici c’est la tendance en Europe à assigner l’Avalonie à tous les terranes péri-gondwaniens situés à l’extérieur de la suture rhéïque lesquels sont caractérisés par un socle relativement juvénile et des âges de zircons détritiques qui comportent des populations mésoprotérozoïques, et ceux situés à l’intérieur de la suture à Cadomia, lesquels sont caractérisés par un socle plus évolué et des âges de zircons détritiques qui correspondent à des sources du craton ouest africain paléoprotérozoïques et plus anciennes.     Bien que l’on estime que les socles non-exposés des terranes d’Avalonie et de Meguma soient très similaires isotopiquement, le couvert sédimentaire de Meguma ne renferme que de rares zircons mésoprotérozoïques, et ce sont plutôt les populations de zircons néoprotérozoïques et paléoprotérozoïques qui dominent, comme c’est le cas pour Cadomia.  Il en ressort que le magma felsique produit par la fusion de croûte dans le terrane de Meguma (par ex. le batholite de South Mountain de 370 Ma env.) est isotopiquement plus jeune (eNd = –5 à –1, TDM = 1.3 Ga) que les roches qu’il recoupe (eNd= –12 à –7, TDM = 1.7 Ga).  Par opposition, le magma felsique produit par la fusion de la croûte dans le terrane d’Avalonie (eNd = –1 à +6, TDM = 0.7–1.2 Ga) est isotopiquement similaire aux roches de son encaissant (eNd = –3 à +4, TDM = 0.9–1.4).     Le profil isotopique du terrane de Meguma, traditionnellement assignée à l’Avalonie,  a aussi été détecté dans la Zone sud-portugaise du sud de l’Espagne.  Cependant, le batholite de Sierra Norte de la Zone sud-portugaise (ca. 330 Ma; eNd = +1 à –3, TDM = 0.9–1.2 Ga) est en moyenne plus jeune que l’encaissant du Dévonien moyen (eNd = –5 à –11) qu’il recoupe, ce qui permet de penser à une extension du terrane de Meguma en Europe.  Les données disponibles du batholite de Cornubian dans le S-O de l’Angleterre (ca. 275–295 Ma; eNd = –4 à –7, TDM = 1.3–1.8 Ga) et des roches métasédimentaires dévono-carbonifères qu’il recoupe (eNd = –8 to –11) permet de penser qu’il pourrait en être de même de cette portion du sud de la Grande-Bretagne (Zone rhénohercynienne) avec laquelle la Zone sud-portugaise est traditionnellement corrélée

T-cell production of matrix metalloproteinases and inhibition of parasite clearance by TIMP-1 during chronic Toxoplasma infection in the brain

Chronic infection with the intracellular protozoan parasite Toxoplasma gondii leads to tissue remodelling in the brain and a continuous requirement for peripheral leucocyte migration within the CNS (central nervous system). In the present study, we investigate the role of MMPs (matrix metalloproteinases) and their inhibitors in T-cell migration into the infected brain. Increased expression of two key molecules, MMP-8 and MMP-10, along with their inhibitor, TIMP-1 (tissue inhibitor of metalloproteinases-1), was observed in the CNS following infection. Analysis of infiltrating lymphocytes demonstrated MMP-8 and -10 production by CD4+ and CD8+ T-cells. In addition, infiltrating T-cells and CNS resident astrocytes increased their expression of TIMP-1 following infection. TIMP-1-deficient mice had a decrease in perivascular accumulation of lymphocyte populations, yet an increase in the proportion of CD4+ T-cells that had trafficked into the CNS. This was accompanied by a reduction in parasite burden in the brain. Taken together, these findings demonstrate a role for MMPs and TIMP-1 in the trafficking of lymphocytes into the CNS during chronic infection in the brain

Association Between Chronic Hepatitis C Virus Infection and Myocardial Infarction Among People Living With HIV in the United States.

Hepatitis C virus (HCV) infection is common among people living with human immunodeficiency virus (PLWH). Extrahepatic manifestations of HCV, including myocardial infarction (MI), are a topic of active research. MI is classified into types, predominantly atheroembolic type 1 MI (T1MI) and supply-demand mismatch type 2 MI (T2MI). We examined the association between HCV and MI among patients in the Centers for AIDS Research (CFAR) Network of Integrated Clinical Systems, a US multicenter clinical cohort of PLWH. MIs were centrally adjudicated and categorized by type using the Third Universal Definition of Myocardial Infarction. We estimated the association between chronic HCV (RNA+) and time to MI while adjusting for demographic characteristics, cardiovascular risk factors, clinical characteristics, and history of injecting drug use. Among 23,407 PLWH aged ≥18 years, there were 336 T1MIs and 330 T2MIs during a median of 4.7 years of follow-up between 1998 and 2016. HCV was associated with a 46% greater risk of T2MI (adjusted hazard ratio (aHR) = 1.46, 95% confidence interval (CI): 1.09, 1.97) but not T1MI (aHR = 0.87, 95% CI: 0.58, 1.29). In an exploratory cause-specific analysis of T2MI, HCV was associated with a 2-fold greater risk of T2MI attributed to sepsis (aHR = 2.01, 95% CI: 1.25, 3.24). Extrahepatic manifestations of HCV in this high-risk population are an important area for continued research

Recent Incarceration, Substance Use, Overdose, and Service Use Among People Who Use Drugs in Rural Communities

Importance: Drug use and incarceration have a substantial impact on rural communities, but factors associated with the incarceration of rural people who use drugs (PWUD) have not been thoroughly investigated. Objective: To characterize associations between recent incarceration, overdose, and substance use disorder (SUD) treatment access among rural PWUD. Design, setting, and participants: For this cross-sectional study, the Rural Opioid Initiative research consortium conducted a survey in geographically diverse rural counties with high rates of overdose across 10 US states (Illinois, Wisconsin, North Carolina, Oregon, Kentucky, West Virginia, Ohio, Massachusetts, New Hampshire, and Vermont) between January 25, 2018, and March 17, 2020, asking PWUD about their substance use, substance use treatment, and interactions with the criminal legal system. Participants were recruited through respondent-driven sampling in 8 rural US regions. Respondents who were willing to recruit additional respondents from their personal networks were enrolled at syringe service programs, community support organizations, and through direct community outreach; these so-called seed respondents then recruited others. Of 3044 respondents, 2935 included participants who resided in rural communities and reported past-30-day injection of any drug or use of opioids nonmedically via any route. Data were analyzed from February 8, 2022, to September 15, 2023. Exposure: Recent incarceration was the exposure of interest, defined as a report of incarceration in jail or prison for at least 1 day in the past 6 months. Main outcomes and measures: The associations between PWUD who were recently incarcerated and main outcomes of treatment use and overdose were examined using logistic regression. Results: Of 2935 participants, 1662 (56.6%) were male, 2496 (85.0%) were White; the mean (SD) age was 36 (10) years; and in the past 30 days, 2507 (85.4%) reported opioid use and 1663 (56.7%) reported injecting drugs daily. A total of 1224 participants (41.7%) reported recent incarceration, with a median (IQR) incarceration of 15 (3-60) days in the past 6 months. Recent incarceration was associated with past-6-month overdose (adjusted odds ratio [AOR], 1.38; 95% CI, 1.12-1.70) and recent SUD treatment (AOR, 1.62; 95% CI, 1.36-1.93) but not recent medication for opioid use disorder (MOUD; AOR, 1.03; 95% CI, 0.82-1.28) or currently carrying naloxone (AOR, 1.02; 95% CI, 0.86-1.21). Conclusions and relevance: In this cross-sectional study of PWUD in rural areas, participants commonly experienced recent incarceration, which was not associated with MOUD, an effective and lifesaving treatment. The criminal legal system should implement effective SUD treatment in rural areas, including MOUD and provision of naloxone, to fully align with evidence-based SUD health care policies.</p

Origin of the Rheic Ocean: Rifting along a Neoproterozoic suture?

The Rheic Ocean is widely believed to have formed in the Late Cambrian–Early Ordovician as a result of the drift of peri-Gondwanan terranes, such as Avalonia and Carolina, from the northern margin of Gondwana, and to have been consumed in the Devonian Carboniferous by continent-continent collision during the formation of Pangea. Other peri-Gondwanan terranes (e.g., Armorica, Ossa-Morena, northwest Iberia, Saxo-Thuringia, Moldanubia) remained along the Gondwanan margin at the time of Rheic Ocean formation. Differences in the Neoproterozoic histories of these peri-Gondwanan terranes suggest the location of the Rheic Ocean rift may have been inherited from Neoproterozoic lithospheric structures formed by the accretion and dispersal of peri-Gondwanan terranes along the northern Gondwanan margin prior to Rheic Ocean opening. Avalonia and Carolina have Sm-Nd isotopic characteristics indicative of recycling of a juvenile ca. 1 Ga source, and they were accreted to the northern Gondwanan margin prior to voluminous late Neoproterozoic arc magmatism. In contrast, Sm-Nd isotopic characteristics of most other peri-Gondwanan terranes closely match those of Eburnian basement, suggesting they reflect recycling of ancient (2 Ga) West African crust. The basements of terranes initially rifted from Gondwana to form the Rheic Ocean were those that had previously accreted during Neoproterozoic orogenesis, suggesting the rift was located near the suture between the accreted terranes and cratonic northern Gondwana. Opening of the Rheic Ocean coincided with the onset of subduction beneath the Laurentian margin in its predecessor, the Iapetus Ocean, suggesting geodynamic linkages between the destruction of the Iapetus Ocean and the creation of the Rheic Ocean

On Divestment

Foreword to On Divestment The writings collected here are an online supplement to a class zine title On Divestment. The zine and online archive were conceived, written, and designed by the members of the Spring 2015 Literature and Environment course (ENGL 374) at the University of Puget Sound. Considerations of timeliness and sustainability encouraged us to keep the size of the printed zine compact by including only excerpts of each author’s work; the zine is in a sense an advertisement for the more substantial body of writing that you find here on Sound Ideas, which reproduces student creative work in its entirety. Informed by our study of works of ecocriticism such as Rob Nixon’s Slow Violence and the Environmentalism of the Poor (Harvard UP, 2011), which explores the role that imaginative writing can play in illuminating ecological issues, our class seized the opportunity of a collaborative final project to see how students’ own writing—whether creative, critical, or some combination of the two—might engage with a topical environmental concern. The selection of a final project was arrived at through a democratic process. Working in groups of five individuals, students presented proposals for a final project, arguing both for the primacy of the environmental concern they selected and the efficacy of the writing task they were asking the class to undertake. All the proposals were excellent, but the class had to settle on a single undertaking; the project that students ultimately selected was the fossil fuel divestment movement, currently a topic of debate on many university campuses, including the University of Puget Sound. Largely led by students, this ongoing environmental movement encourages colleges and universities to divest their endowment holdings from companies whose primary business is fossil fuel. Since we knew from recent reportage in The Trail that UPS’s own ECO Club is advocating for fossil fuel divestment, we invited ECO Club representatives to speak to the class. From their visit, we learned about the broad contours of the divestment movement. Observing that the majority of scientists understand anthropogenic climate change to be the result of burning fossil fuels, the divestment movement argues that colleges and universities should exert pressure on these companies by withdrawing their investments from them. Several universities have already made commitments to divest some component of their endowment, among them Stanford University, Pitzer College, and the University of Glasgow, and campaigns to do so are underway at other institutions of higher learning, as well as many cities and municipalities. In formalizing the class proposal into an assignment, the terms were intentionally crafted to remain open-ended and non-prescriptive. Students were invited simply “to create a work of literature or literary analysis that engages with the issue of university fossil fuel divestment.” (Students could also opt out of the zine and write a more conventional final essay). Here are some excerpts from an email that I sent to the class elaborating on this non-traditional assignment. There\u27s a quotation by W.B. Yeats that strikes me as relevant here: Out of the quarrel with others we make rhetoric; out of the quarrel with ourselves we make poetry. What I understand Yeats to mean is that honest creative writing explores its subject, rather than argues a pre-established position. (For his word poetry in that quotation, you could equally substitute drama, or fiction, creative nonfiction, etc.) Our goal is to write literature, not propaganda . . . . While the work you create should shed light on some aspect of the divestment issue, it needn\u27t do so directly. In fact, it’s possible to shed light on the issue without even mentioning the word “divestment.” Consider, for example, the first novel we read this semester, Margaret Atwood’s Oryx and Crake. That novel engages with a host of environmental topics, among them global climate change, genetic engineering, population growth, the treatment of animals, and environmental justice. It doesn\u27t tell the reader what to do or think about any of these issues; rather, it explores them imaginatively, but it does so in a way that I believe encourages readers to be more reflective about each of those issues than they were before starting the novel. It sheds light on these issues. [K]eep in mind that this assignment does not expect that you will take a particular position. It does not assume that you will create a work of literature or literary criticism that is “for” fossil fuel divestment. (I\u27m not even sure that a work of art can ever be “for” or “against” a particular action. Is Oryx and Crake for or against the human manipulation of the environment? Who knows?—it\u27s a work of imaginative writing that tells a story. Readers can engage their own sense of values based upon the encounter with the imaginative work). I hope that this advice is helpful and that you feel authorized to write freely. I created the opportunity for the assignment because I believe that your voice—both individually and collectively—does matter and I wanted to facilitate a way for it to be heard, in however modest a fashion. What that voice says is entirely up to you. Those twenty voices from the class combine to form the collective voice you encounter here in the Sound Ideas archive On Divestment. On behalf of the writers and critics in ENGL 374, I invite you explore these remarkable poems, short stories, essays, and plays in their entirety. Best wishes, Prof. William Kupinse Department of Englis