Objectives
Mitochondrial methionyl‐tRNA formyltransferase (MTFMT) is required for the initiation of translation and elongation of mitochondrial protein synthesis. Pathogenic variants in MTFMT have ...been associated with Leigh syndrome (LS) and mitochondrial multiple respiratory chain deficiencies. We sought to elucidate the spectrum of clinical, neuroradiological and molecular genetic findings of patients with bi‐allelic pathogenic variants in MTFMT.
Methods
Retrospective cohort study combining new cases and previously published cases.
Results
Thirty‐eight patients with pathogenic variants in MTFMT were identified, including eight new cases. The median age of presentation was 14 months (range: birth to 17 years, interquartile range IQR 4.5 years), with developmental delay and motor symptoms being the most frequent initial manifestation. Twenty‐nine percent of the patients survived into adulthood. MRI headings in MTFMT pathogenic variants included symmetrical basal ganglia changes (62%), periventricular and subcortical white matter abnormalities (55%), and brainstem lesions (48%). Isolated complex I and combined respiratory chain deficiencies were identified in 31% and 59% of the cases, respectively. Reduction of the mitochondrial complex I and complex IV subunits was identified in the fibroblasts (13/13). Sixteen pathogenic variants were identified, of which c.626C>T was the most common. Seventy‐four percent of the patients were alive at their last clinical review (median 6.8 years, range: 14 months to 31 years, IQR 14.5 years).
Interpretation
Patients that harbour pathogenic variants in MTFMT have a milder clinical phenotype and disease progression compared to LS caused by other nuclear defects. Fibroblasts may preclude the need for muscle biopsy, to prove causality of any novel variant.
The brown Lygodium defoliating moth, Neomusotimaconspurcatalis Warren (Lepidoptera: Crambidae), was released beginning in 2008 to control Old World climbing fern, Lygodium microphyllum (Cav.) R. Br ...(Polypodiales: Lygodiaceae). The moth readily established in Jonathan Dickinson State Park, but at other sites populations remained at low densities or were locally extirpated. In 2012 and 2013, we recovered N. conspurcatalis populations at all original release sites except Everglades National Park and those treated with herbicide. The original releases of 4,000 or more individuals per site were entirely successful, pointing to a strategy that focuses on numbers at this target level or beyond for future releases in Florida.
Recentering the City LAKE, ROBERT W.
International journal of urban and regional research,
March 2006, Volume:
30, Issue:
1
Journal Article
Peer reviewed
In The City and the Grassroots, Manuel Castells recentered the city as the site of distinctively urban social movements and reaffirmed the role of purposive social action in constructing a ...distinctively urban space. Although Castells’ recitation of five centuries of urban political activism documents the consistent failure of such movements to achieve their goals, his account is persistently optimistic on at least three counts. First, recentering the city reminds us that, despite the failure of transitory political movements, the city endures as an opportunity for renewed political activism. The continual possibility of change offered by the city's ontological persistence is separate from the fate of any given political intervention. Second, regardless of its specific success or failure, each episode of urban activism establishes a new context for the next encounter, its legacy persisting in the collective memories — the stock of mnemonic capital — of which the city is the repository. Third, Castells’ emphasis on political agency affirms that, while all action is ephemeral, its constitutive re‐enactment ceaselessly provides openings for insurgency and transgression. This optimistic message is worth repeating today.
State restructuring through decentralization, privatization, and related processes has prompted the growth of the non-profit sector as a 'shadow state' increasingly responsible for social service ...delivery and community development. In this context, the question arises as to how citizenship, defined as inclusion in a polity through the distribution of rights and resources, is realized within the shadow state. If non-profit organizations are assuming functions of the state but access to the shadow state is unevenly distributed, the result may be selective disenfranchisement or differential citizenship. This paper examines the nature of differential access to citizenship within the shadow state by looking at the practices and contexts of non-profit community development corporations (CDCs) in the city of Newark, New Jersey. The shadow state is affected by structural and contextual influences including financial, policy, and political factors that produce differential organizational capacity, uneven spatial coverage, client selectivity, inadequate program support, unrecognized need, and unconsidered clients' preferences. These contextualized practices in turn result in differential access to citizenship in the shadow state. Solutions to the problem of differential citizenship require improvements in the structural and contextual conditions influencing the scope and capacity of the non-profit sector.
Mutations in the “a” determinant of the surface gene have been associated with failure of hepatitis B immunoglobulin (HBIg) prophylaxis. We compared sequences from the surface and polymerase regions ...of hepatitis B virus (HBV) from 4 patients who failed high‐dose HBIg therapy with two control groups: HBIg‐treated patients who remained hepatitis B surface antigen (HBsAg)‐negative (n = 4) and HBV‐infected transplant recipients who never received HBIg (n = 4). Mutations within the surface and overlapping polymerase region were more common in patients failing HBIg than controls (P = .03), and mutations in the region of the “a” determinant were present only in patients failing HBIg. To examine the relationship between HBIg failure and duration of therapy, five additional treatment failures from a second transplantation center were sequenced (total with HBIg failure = 9). Mutations in the “a” determinant developed in 1 of 3 patients receiving HBIg for less than 6 months compared with 5 of 6 patients failing HBIg after 6 months of therapy (P = .23). The most frequently identified amino acid substitution was glycine to arginine at position 145 (present in 4 of 6 patients who failed HBIg after at least 6 months of treatment). A unique mutation within the YMDD motif (methionine to leucine) was present in 1 patient who failed HBIg treatment and who received a short course of ganciclovir. We conclude that the emergence of mutations in the “a” determinant accounts for some, but not all, treatment failures in patients receiving HBIg prophylaxis. Mutations in other regions of the S gene were more common in patients failing HBIg than controls, suggesting that domains other than the “a” determinant may be important.
This review was designed to determine whether “high-dose” steroid therapy (⩾20 mg prednisone/day) increases the likelihood of anastomotic complications after restorative proctocolectomy with ileal ...pouch–anal anastomosis (IPAA). The hospital records of 100 patients undergoing proctocolectomy with IPAA were reviewed. Patient characteristics were analyzed to determine what factors were associated with higher rates of anastomosis-related complications. Seventy-one of our patients were given diverting ileostomies, whereas the remaining 29 underwent a single-stage procedure. Fifty-four percent of the patients in our review were taking steroids preoperatively, 39 of whom were on high-dose therapy. The overall anastomosis-related complication rate was 14%. There was no significant difference in complication rates with respect to age, steroid use, steroid dose, use of a diverting ileostomy, type of anastomosis, duration of disease, or presence of backwash ileitis. A trend toward higher leakage rates was found in patients undergoing single-stage procedures (10.3% vs. 2.8%,
P
=
0.14) as well as in patients undergoing single-stage procedures on high-dose steroids (22% vs. 5.0,
P
=
0.22). Nevertheless, neither of these trends was found to be statistically significant, which was likely influenced by the small sample size. Our data suggest that there may be an increase in anastomotic leakage rates in patients on high-dose steroids undergoing a single-stage proctocolectomy with IPAA. Nevertheless, our rate was not as high as the rates seen by other investigators and did not reach statistical significance. During preoperative counseling, patients on high-dose steroids should be informed of this uncertain but real risk of anastomotic leakage.
Bring back big government Lake, Robert W.
International journal of urban and regional research,
December 2002, Volume:
26, Issue:
4
Journal Article
Peer reviewed
Despite widespread claims of its demise, the national state is the scale of the state institution best able to marshal the political, discursive and material resources necessary to achieve goals of ...social justice, defined as a decrease in income inequality, at local, national and global scales. The appearance of the withering away of the state is deceptive, since it is the state itself that is enacting the distribution of functions that some observers interpret as a reduction in state power. The arguments for a return of big government are both strategic and tactical. Strategically, central government has been responsible for every major social policy advance in the United States in the twentieth century. Tactically, the institutions comprising decentralized governance, including local governments, non–profit foundations and community–based organizations, are inadequate to the task. The role of big government in pursuit of social justice entails discursive and regulatory functions, each in turn suggesting an attendant political project for academics and activists. What is at stake is not a quantitative redistribution of state power but a qualitative redirection of the purposes to which that power is applied. Uncritical insistence on the end of the nation state may create a self–defeating self–fulfilling prophecy that conceals important opportunities for political realignment.
L’Etat nation est à la meilleure échelle pour mobiliser les ressources politiques, discursives et matérielles nécessaires à la poursuite de la justice sociale, définie comme la réduction des inégalités de revenu aux échelles locales, nationales et globales, et ce malgré les affirmations répandues sur le retrait de l’Etat. L’apparence d’effacement de l’Etat est trompeuse puisque c’est l’Etat luui même qui organise la réallocation des fonctions que certains observateurs interprètent comme une réduction du pouvoir de l’Etat. L’argument en faveur d’un retour du ‘big government’ sont à la fois stratégiques et tactiques. D’un point de vue stratégique, le gouvernement central a été responsable de toutes les grandes avancées sociales du Xxème siècle aux USA. Sur le plan tactique, les institutions de gouvernance décentralisée comprenant le gouvernement local, les fondations à but non lucratif et les organisations communautaires ne peuvent pas faire face à ces tâches. Le rôle du gouvernement dans la poursuite de la justice sociale comprend des fonctions régulatives et discursives, chacune d’entre elle renvoyant à des projets politiques pour les activistes et les universitaires. Ce n’est pas la réallocation de l’autorité qui est en jeu mais une réorientation des objectifs du pouvoir. L’accent mis sans réserve sur la fin de l’Etat nation pourrait crééer une prophétie auto–créatrice auto–défaitiste qui dissimulerait les vraies opportunités de réorientation politique.
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