Late Episodes Research Articles

Oxybutynin for Antidepressant-Induced Hyperhidrosis

Back to table of contents Previous article Next article Communications and UpdatesFull AccessOxybutynin for Antidepressant-Induced HyperhidrosisKoen P. Grootens, M.D., Ph.D.Koen P. GrootensNijmegen, the NetherlandsSearch for more papers by this author, M.D., Ph.D.Published Online:1 Mar 2011https://doi.org/10.1176/appi.ajp.2010.10091348AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Hyperhidrosis, or excessive sweating, can be an uncomfortable and embarrassing side effect of antidepressants. It is estimated to occur in 14% of patients taking tricyclic antidepressants (1). The presumed mechanism of tricyclic antidepressant-induced sweating is the inhibited reuptake of norepinephrine, leading to the stimulation of peripheral adrenergic receptors (2).Sweat glands are innervated by peripheral sympathetic nerves, which are mediated by acetylcholine. Oxybutynin, an anticholinergic drug that is registered for urge incontinence, has shown to be effective in the treatment of excessive sweating in some cases (3) but has not yet been reported to be effective in cases of antidepressant-induced sweating. Here, I present two cases in which oxybutynin was successfully introduced to decrease excessive sweating.Patient A is a 59-year-old man with a history of recurrent episodes of panic disorder, for which he had used paroxetine, venlafaxine, and escitalopram as well as high doses of oxazepam in the past. He was admitted to the hospital because of a severe depressive episode with suicidal ideation. The depression was successfully treated with clomipramine, 100 mg/day, which was effective for the treatment of panic attacks as well. Although he sweated all over his body, he was willing to continue clomipramine monotherapy after discharge. Lowering the dosage did not change the situation, nor did treatment with cognitive-behavioral therapy. Finally, a trial with oxybutynin, 2.5 mg b.i.d., relieved the hyperhidrosis completely, without any side effects.Patient B is a 60-year-old man with recurrent severe depressive episodes with psychotic symptoms and agitation. Typical for his disorder are the rapid onset of relapse and the severity of agitation, which in the past required hospitalization and seclusion. In the latest episode he was treated with clomipramine, 75 mg/day, and olanzapine, 15 mg/day, but he suffered from severe hyperhidrosis. A switch from olanzapine to haloperidol did not change the hyperhidrosis. Later, 800 mg/day of lithium was successfully added for the treatment of his depressive symptoms. Oxybutynin, 5 mg t.i.d., was added to his treatment and relieved his hyperhidrosis without side effects.There are several preferential strategies to treat hyperhidrosis, such as lowering the dosage or altering the dosing schedule, changing clothing or food habits, or regulating anxiety (2). In the present two cases, these strategies were unsuccessful and oxybutynin maintenance treatment was introduced. With its rapid, short-term effect (within an hour), oxybutynin could also be considered “as needed” in specific social situations. One should be careful in dosing to avoid anticholinergic side effects such as constipation, urinary retention, and blurred vision. Although placebo-controlled research is necessary, the cases reported here suggest that adding oxybutynin to antidepressants can be a simple and effective treatment option for hyperhidrosis.Nijmegen, the NetherlandsDr. Grootens reports no financial relationships with commercial interests.This letter was accepted for publication in December 2010.

Antithymocyte treatment of steroid-resistant acute rejection in renal transplantation

To evaluate the outcome of early (ER <3 months) and late (LR >3 months) episodes of corticosteroid resistant acute allograft rejection (CRR) treated with anti-thymocyte globulin (ATG) in pediatric renal allograft recipients. Retrospective study of 15 children, mean age 13.2 y, who received ATG for the treatment of biopsy proven CRR over a 15 year period. Seven children received ATG for ER (median 26 days post transplantation) and 8 for LR (median 763 days). There was a significant improvement in the 3 month eGFR (70.3 ml/min/1.73m(2), SD 22.3, p = 0.018) when compared with the value prior to ATG treatment (23.3 ml/min/1.73m(2), SD 10.2) in the ER group. In the LR group (4 DSA positive) there was no improvement in the eGFR at 3 months (42 ml/min/1.73m(2), SD 10.5, p = 0.32) when compared with the value prior to ATG (38 ml/min/1.73 m(2), SD 9.7). At final review, eGFR in the ER group was 72.3 ml/min/1.73m(2) (SD 33) vs. 37.7 ml/min/1.73m(2) (SD 17.9) in the LR group after a mean follow up of 10.4 y and 1.2 y, respectively. ATG therapy in CRR is associated with reversal of rejection and excellent graft outcome in children with ER. The benefits remain uncertain in LR, the etiology of which is multifactorial.

Steroid-resistant acute allograft rejection in renal transplantation

Steroid-resistant rejection after pediatric renal transplantation forms a rare but severe complication with a guarded prognosis particularly if this occurs late after transplantation. There is a paucity of data on how to manage these challenging rejection episodes, particularly in the pediatric literature. Mohan Shenoy et al. published a case series of 15 patients who were treated with anti-thymocyte globulin for steroid-resistant acute allograft rejection over a 15-year period in a single center in this issue of Pediatric Nephrology. While the results for the early rejection group were encouraging, the results in the eight patients with late rejection episodes after transplantation were unfavorable and afflicted with a high incidence of side-effects. Important diagnostic tools such as C4d staining of the renal transplant biopsy and the measurement of donor-specific antibodies were underutilized. The editorial reviews the importance of the differentiation between humoral and cellular rejection and the challenges of treating late antibody-mediated acute rejection in these patients. A multi-center approach is required to establish a registry of these events and ideally prospective randomized interventions should be designed to provide some evidence base for the management of this challenging complication after pediatric renal transplantation.

Fast-Follower Industrial Dynamics: The Case of Taiwan's Emergent Solar Photovoltaic Industry

The world is on the cusp of major transformations of energy systems, with solar photovoltaic (PV) systems providing one of the most promising alternatives to fossil fuels. Amongst the countries moving to take advantage of the new production possibilities thus being opened up is Taiwan, employing in this new sector its characteristic strategies of fast followership that it has perfected in earlier industrial shifts involving semiconductors, ICT products and flat panel displays. This paper provides an interim assessment of Taiwan's early entry strategies, involving a focus on mainstream crystalline silicon solar cells, as well as entry into emerging niche sectors such as thin-film second-generation cells and concentrated solar cells utilizing novel semiconductor materials. Taiwan firms’ fast-follower strategies are highlighted and assessed in light of the literature on industrial dynamics and catch-up processes generally. The paper makes a contribution to theory in building nine propositions regarding fast followership, based on prior industrial experiences and this latest episode in the solar PV industry. Taiwan's strategies as a model for China are discussed, while the paper proposes Taiwan as an alternative to the “closed” and “open” models of photovoltaic diffusion identified for Japan and the USA.

Introduction: Religion and Freedom of Expression

Tensions between religion and freedom of expression have a long pedigree. Given the central place that religious faith has occupied in the history of humanity and given the special status humanity has ascribed to the sacred and the divine, it could hardly have been otherwise. Contemporary controversies concerning the relative claims of religion and free expression might therefore be seen as no more than the latest episodes in an argument that has been conducted for two or more millennia. But the history of that argument is a changing history and its present character differs from its past. While in some societies the shielding of religion from free expression continues to be defended as a means of maintaining truth and preventing its corruption, that form of defence has been largely abandoned in western societies. In those societies, religious diversity is now accepted as a legitimate state of affairs as well as a matter of fact, so that, at least in public argument, no denomination and no faith can claim protection simply in virtue of the truth of its beliefs. As the articles that make up this collection indicate, arguments about faith and free expression now pivot on different sorts of concern, such as the recognition due to people’s identities, the prevention of offence, insult and hatred, and the maintenance of public order and social cohesion. Appeals to the truth and its promotion are now more likely to come from those who want religion to feel the full force of free expression. Arguments about the respective claims of religion and free expression are also now conducted in a world in which there is a large measure of ‘unbelief’, which encompasses a wide variety of positions from dogmatic atheism to mere failure to be engaged by religion. They take place too in a world in which we are used to distinguishing between the proper spheres of the religious and the secular. Against that background, it is easy to gain the impression that the battle lines in arguments

Junk Culture and the Post-Genomic Age

Junk Culture and the Post-Genomic Age Allison Carruth (bio) Review of Thierry Bardini, Junkware. Minneapolis: U of Minnesota P, 2011. Print. In the spring of 1953, James Watson and Francis Crick published a series of papers in Nature that led them to claim that DNA is "the molecular basis of the template needed for genetic replication" (qtd. in Watson 246). The papers paved the way for Watson and Crick to receive the 1962 Nobel Prize in Physiology, in turn validating what Crick had famously termed the "Central Dogma": the view that information, in the form of biochemical blueprints, flows one-way from DNA to RNA to proteins. This causal process continues to inform the paradigm in molecular biology according to which DNA is "the most important component of the cell, its 'master plan'" (Strasser 493). What the Central Dogma has struggled to accommodate, however, is so-called junk DNA: those DNA bases that do not code for protein (some 98.5% in the human genome) and hence appear to be excessive, or to have no genetic function (Bardini 20, 29-30). Thierry Bardini's Junkware, a recent title from Minnesota's Posthumanities series, interrogates this very paradigm by considering the biological fact and cultural significance of junk DNA. For Bardini, junk DNA is both master trope and fringe element of an era in which human beings are becoming "junkware": "a new kind of slave[,] enslaved in our code itself" and subject to a "disposable and recyclable" society of workers, consumers, and spectators (7, 9). Bardini defines junk as "the quintessential rhizomatous genus" of Homo nexus, an emergent subjectivity at once individuated and networked (13). To develop this argument, Part One of Junkware ("Biomolecular Junk") traces the cybernetic view of biological life through its "blind spot" of junk DNA. In Part Two ("Molar Junk: Hyperviral Culture"), Bardini shifts from the social study of modern genetics to offer a cultural theory of junk more widely construed. Throughout, his method is one of accumulation, aggregation, and critique. Junkware sifts through an array of materials that includes science fiction, online wikis, Google search results, epistemology, cybernetics, critical theory, and mass media coverage of everything from the Human Genome Project to gene therapy. A cross-disciplinary scholar, Bardini's voice in Junkware ranges from that of the high theorist to that of the pop culture critic to that of the social scientist. Bardini's project makes two interventions: one in the discourse of biopolitics and one in the history of genetics. As for the former, Bardini sees the ultimate horizons of capitalism as the "invention of genetic capital" and the systematization of "living money" in the form not only of animal and human bodies but also of tissues, organs, and genes (11). Here, we can situate Junkware within recent work on what sociologist Nikolas Rose and others term "life itself." The thesis of Junkware resonates most clearly with Nicole Shukin's contention in Animal Capital that late capitalism has literalized commodity fetishism by turning biological life into currency, while the free market system has simultaneously become vulnerable to "novel diseases erupting out of the closed loop" of biocapital (16-19). In Tactical Media, Rita Raley suggests that late capitalism and critical theory participate in a feedback loop, whereby the material procedures of late capital both determine and are determined by the theoretical terms of biopolitical critique. Raley observes, for example, that capitalist ideologies of mutation and adaptation cross-pollinate with postmodern theory, as in Fredric Jameson's argument that late capitalism operates like a biological virus (129). In Junkware's historiography of genetics, Bardini engages the work of both Michel Foucault and Gilles Deleuze to claim that twenty-first century society morphs beyond both the disciplinary societies of the industrial era and the control societies of the post-industrial era. In "Postscript on the Societies of Control," Deleuze argues that the third stage of capitalist society hinges on "floating rates of exchange" and "a continuous network" in which the individual and the collective "orbit" one another. Seeing a fourth stage of capitalism on the horizon, Bardini writes, "the latest episode in the modern civilization . . . is the cybernetic decoding and organizing of the flows of...

Late Viral Infections After Cord Blood Transplantation: Comparison with Unrelated Bone Marrow Transplantation

AbstractAbstract 1260Although the efficacy of cord blood transplantation (CBT) from unrelated donors as viable alternative for patients in need of hemtopoietic stem cell transplantation (HSCT) is supported by growing evidences, viral infections related to delayed immune reconstitution remains important problems for further improvement of clinical outcomes. To evaluate incidences and outcomes of late viral infections after CBT by comparison with those after unrelated bone marrow transplantation (uBMT), we retrospectively analyzed the records of 281 Japanese adult patients who underwent allogeneic unrelated HSCT for the first time at the Toranomon Hospital between January, 2002 and March, 2010, and who survived more than 100 days after HSCT without the lost-to-follow-up or retransplantation before day 100. Between 50 days and 5 years after HSCT, 116 patients had at least one late infectious episode with a cumulative incidence of 52.2%, at a median of 157 (50-1597) days after HSCT. The 5-year cumulative incidence of any late viral infections was greater in CBT versus uBMT recipients (60.7% vs. 42.2%, respectively; P=0.039, Figure 1). Thirty-three patients (28.4%) had 2 or more episodes caused by different viruses, and a total of 152 late infectious episodes were documented. The median onset of the episodes was similar between the both groups (median onset 226 days vs 222 days, P=0.89). The most common late viral infection is varicella-zoster virus (VZV) reactivation, accounting for 28.8% (disseminated 10, localized 34), followed by hemorrhagic cystitis associated with adeno- and/or BK viruria (28.2%), cytomegalovirus (CMV) diseases (16.4%; gastrointestinal diseases 23, retinitis 1, pneumonia 1), and respiratory tract infections caused by influenza virus, parainfluenza virus or respiratory syncytial virus (15.8%; upper 26, lower 8), and Epstein-barr virus lymphoproliferative diseases (4.6%). The remaining 10 infectious episodes were caused by relatively rare type of viruses including herpes simplex virus, JC virus, measles virus, mumps virus, norovirus and parvovirus, all of which occurred only in CBT recipients. Of all these viral infections, only VZV reactivation developed significantly more frequent in CBT than in uBMT recipients (P=34.0% vs 17.0%, P=0.023). There was no difference of dissemination rate between the both groups, and all the patients responded well to treatment with antiviral agents. The late viral infection was a primary cause of death in 3 episodes, all of which were pneumonia caused by CMV, influenza virus and parainfluenza virus. The 5-year incidence of infection-related mortality did not differ between CBT and uBMT recipients (0.7% vs 3.1%, P=0.46). Non-relapse mortality occurred in 11.8 % and 16.4 % patients in the CBT and uBMT groups (P=0.71). These findings suggested that cord blood might be as an acceptable and useful stem-cell source as bone marrow from unrelated donors in terms of risks of viral infection in the late posttransplant period. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Paleo-fluids characterisation and fluid flow modelling along a regional transect in Northern United Arab Emirates (UAE)

In the Northern Emirates, Jurassic and Lower Cretaceous platform carbonates of the Musandam parautochthonous units are tectonically overlain by siliciclastic units of the Hawasina–Sumeini allochthon, which derive from the former paleo-slope domain and a more distal basinal portion of the Arabian margin of the Tethys, respectively. All these tectonic units display numerous evidences of paleo-fluid circulations, accounting for dolomitisation and recrystallisation of the rock matrix (Musandam Platform units), as well as cementation of fractures. Polymict breccias of Upper Cretaceous Ausaq Formation which underlay the sole thrust of the Hawasina–Sumeini allochthon also record episodes of hydraulic fracturing, whereas fluid inclusion data indicate precipitation at high temperature in relation to paleo-fluid flow. Petrography of thin-sections (conventional and cathodoluminescence microscopic techniques) as well as fluid inclusion and stable isotopes analyses, were combined with micro-tectonic studies. These analytical data document (1) the paragenetic sequence of diagenetic products for the Musandam Platform (which constitutes a carbonate reservoir analogue) and Sumeini units of the Dibba Zone, as well as (2) the nature of the paleo-fluids circulating along fractures and the sole thrust of the Hawasina–Sumeini allochthon. The main results of this petrographic approach are qualitative, evidencing (1) the rapid and vertical transfer of hot fluids in the vicinity of the former slope to platform transition, accounting for episodes of hydrothermal dolomitisation, as well as (2) early (i.e. pre-orogenic) and late (i.e. post-orogenic) episodes of emersion of the carbonate units, accounting for additional interactions with meteoric fluids and karstification. In order to better link these diagenetic events with the overall burial, thermal and kinematic evolution of the Arabian margin, basin modelling with Ceres2D, including fluid flow and pore-fluid pressure modelling, was subsequently performed along a regional transect (D4) located in the vicinity of the samples localities and cross-cutting the Northern Oman Mountains from Dibba in the east up to the Arabian Gulf in the west. New subsurface constraints provided by deep seismic profiles were used to constrain the architecture of the cross-section, and to test various hypotheses on the lateral and vertical connection, timing and hydrodynamic behaviour of the faults. This Ceres basin modelling also provides new quantitative estimates of the paleo-fluid pathways, of the timing and velocities of the fluid transfers and of the evolution of pore-fluid pressures. Ultimately, this integration of petrographic studies on surface samples and coupled kinematic and fluid flow basin modelling provides an updated scenario for the succession of tectonically controlled episodes of fluid rock interactions, namely dolomitisation and karstification recorded in the Mesozoic platform carbonates of the Northern Emirates.

ATG‐Fresenius Treatment and Low‐Dose Tacrolimus: Results of a Randomized Controlled Trial in Liver Transplantation

We report the results of a prospective randomized controlled trial in liver transplantation assessing the efficacy and safety of antithymocyte globulin (ATG-Fresenius) plus tacrolimus monotherapy at gradually decreasing doses. Patients were randomized to either: (a) standard-dose tacrolimus plus steroids;or (b) peritransplant ATG-Fresenius plus reduced-dose tacrolimus monotherapy followed by weaning of tacrolimus starting 3 months after transplantation. The primary end-point was the achievement of very low-dose tacrolimus (every-other-day or once daily dose with <5 ng/mL trough levels) at 12 months after transplantation. Acute rejection occurring during the first 3 months after transplantation was more frequent in the ATG group (52.4% vs. 25%). Moreover, late acute rejection episodes occurred in all recipients in whom weaning was attempted and no recipients reached the primary end-point. This motivated the premature termination of the trial. Tacrolimus trough levels were lower in the ATG-Fresenius group but no benefits in terms of improved renal function, lower metabolic complications or increased prevalence of tolerance-related biomarkers were observed. In conclusion, the use of ATG-Fresenius and tacrolimus at gradually decreasing doses was associated with a high rate of rejection, did not allow for the administration of very low doses of tacrolimus and failed to provide detectable clinical benefits. ClinicalTrials.gov identifier: NCT00436722.

A revision of the stratigraphy and geology of the south-western part of the Crotone Basin (South Italy)

The Crotone Basin, located on a stack of nappes piled up during the late Paleogene-Neogene, formed in the late Neogene to Quaternary as a forearc basin of the Ionian arc-trench system. The process of slab rollback caused rapid trench migration, resulting in an extensionaltranstensional regime persisting most of the time in the forearc area.The late Neogene tectonic evolution was strongly influenced by a NW-directed fault system, interpreted as basement wrench faults leading to partitioning of the basin into separate sub-basins subject to differential subsidence and mutual displacements. Major sequences identified in the area are regarded as tectono-stratigraphic sequences (TSS). The first of them was laid down in the late Serravallian (?) - Tortonian - early Messinian, during the basin opening stage and is bounded at the top by an erosional unconformity, which may be correlated with the well-known intra-Messinian event of the Mediterranean Salinity Crisis. The second TSS, of middle to late Messinian age, is characterized by strongly syntectonic deposits mostly derived from cannibalization of the lower Messiniansuccession, first infilling extensional troughs, then involved in an episode of sinistral transpression along the NW-trending fault system, which generated local overthrusts, sealed by a late Messinian erosional unconformity. The Messinian tectonics probably reflects the interplay between the processes linked to the kinematics of the Calabria block and those triggered by the Salinity Crisis. The erosional unconformity is overlain by widespread coarse fluvial conglomerates, which are the first onlapping term of the third TSS, represented by uppermost Messinian to lower Zanclean deposits, laid down in an extensional-transtensional regime. This TSS was closed by an important late Zanclean episode of dextral transpression along the NW-trending fault system, leading to inversion of the formerbasins, and limited SW-verging thrusts on fault-restraining bends.The unconformity sealing the structures has a clear expression in the northern, marginal part of the Crotone Basin and correlates downbasin with a conformable surface. The fourth TSS is characterized by a long-lasting phase dominated by extension-transtension, leading to high subsidence rate during the latest Zanclean to Early Pleistocene, and accommodating a thick succession of slope mudstones including clusters of diatomaceous bands mostly in the D. tamalis and D. brouweri Zones. In the northern part of the Crotone Basin two phases of drowning separated by an uplift pulse at ca. 2.55 Ma can be recognized, the second of which was a dramatic collapse, between 2.3 and 2.1 Ma. The fifth TSS is bounded at the base by an unconformity at the transition between «large» and «small» GephyrocapsaZones, i.e. at around 1.1-1.2 Ma, correlating basinwards with a conformable surface. The unconformity is erosional and locally angular in the marginal part of the basin, where it seals structures generated by a contractional event documented also elsewhere in the Calabria block. This event, which is accompanied by a strikeslip component, is inferred to be coeval to the Lower Pleistocene important transpressional episode along the Pollino shear system,which led to release of the Calabria block from the southern Apennines.The fifth TSS is characterized by resumed dextral transtension in the Middle Pleistocene along right-stepping NW-trending faults. This episode generated minor pull-apart sub-basins, showing spectacular growth structures in their infilling successions, which developed with shoaling trend up to inferred Marine Isotope Stages 9-8. The onset of shoaling trend was diachronous, being remarkably younger in the southern sub-basin. In the late Middle Pleistocene to Recent times extensional tectonics was dominating, accompanied by local gravity gliding towards the Ionian Sea, arguably triggered by increase in topographic gradient following hinterland uplift, and implying the activation of a linked, thin-skinned extensional and contractional NE- to NNE-directed fault system, with detachment surface possibly soling into Messinian evaporitic-mudstone deposits. It is concluded that the geologic evolution of the investigated forearc area was characterized by an alternation of long-lived stages of extension-transtension expressed by prolonged subsidence preceded by uplift pulses, and short-lived episodes of contraction-transpression.Major drowning episodes in the forearc area are thought to be coeval to the main phases of spreading in the Tyrrhenian basin.

Stratigraphy, mineralogy, and origin of layered deposits inside Terby crater, Mars

The 174 km diameter Terby impact crater (28.0°S–74.1°E) located on the northern rim of the Hellas basin displays anomalous inner morphology, including a flat floor and light-toned layered deposits. An analysis of these deposits was performed using multiple datasets from Mars Global Surveyor, Mars Odyssey, Mars Express and Mars Reconnaissance Orbiter missions, with visible images for interpretation, near-infrared data for mineralogical mapping, and topography for geometry. The geometry of layered deposits was consistent with that of sediments that settled mainly in a sub-aqueous environment, during the Noachian period as determined by crater counts. To the north, the thickest sediments displayed sequences for fan deltas, as identified by 100 m to 1 km long clinoforms, as defined by horizontal beds passing to foreset beds dipping by 6–10° toward the center of the Terby crater. The identification of distinct sub-aqueous fan sequences, separated by unconformities and local wedges, showed the accumulation of sediments from prograding/onlapping depositional sequences, due to lake level and sediment supply variations. The mineralogy of several layers with hydrated minerals, including Fe/Mg phyllosilicates, supports this type of sedimentary environment. The volume of fan sediments was estimated as >5000 km 3 (a large amount considering classical martian fan deltas such as Eberswalde (6 km 3)) and requires sustained liquid water activity. Such a large sedimentary deposition in Terby crater is characteristic of the Noachian/Phyllosian period during which the environment favored the formation of phyllosilicates. The latter were detected by spectral data in the layered deposits of Terby crater in three distinct layer sequences. During the Hesperian period, the sediments experienced strong erosion, possibly enhanced by more acidic conditions, forming the current morphology with three mesas and closed depressions. Small fluvial valleys and alluvial fans formed subsequently, attesting to late fluvial processes dated as late Early to early Late Hesperian. After this late fluvial episode, the Terby impact crater was submitted to aeolian processes and permanent cold conditions with viscous flow features. Therefore, the Terby crater displays, in a single location, geologic features that characterize the three main periods of time on Mars, with the presence of one of the thickest sub-aqueous fan deposits reported on Mars. The filling of Terby impact crater is thus one potential “reference geologic cross-section” for Mars stratigraphy.

Hercynian post-collisional magmatism in the context of Paleozoic magmatic evolution of the Tien Shan orogenic belt

The Hercynian Tien Shan (Tianshan) orogen formed during Late Palaeozoic collision between the Karakum–Tarim and the Kazakhstan paleo-continents. In order to constrain timing of Hercynian post-collisional magmatism, 27 intrusions were sampled for U–Pb zircon dating along a ca. 2000 km – long profile in Uzbekistan and Kyrgyzstan. The samples were dated utilizing sensitive high resolution ion microprobe (SHRIMP-II). The obtained ages, together with previously published age data, allowed the timing of Hercynian post-collisional magmatism to be constrained and interpreted in the context of the Paleozoic magmatic evolution of the region. Apart from Hercynian post-collisional magmatism, two older magmatic episodes have been recognized, and the following sequence of events has been established: (1) approximately 10 Ma after cessation of continuous Caledonian magmatism a number of Late Silurian–Early Devonian intrusions were emplaced in the Middle and Northern Tien Shan terranes between 420 and 390 Ma. The intrusions probably formed in an extensional back arc setting during coeval subduction under the margins of Caledonian Paleo-Kazakhstan continent; (2) the next relatively short Late Carboniferous episode of subduction under Paleo-Kazakhstan was registered in the Kurama range of the Middle Tien Shan. Calc-alkaline volcanics and granitoids with ages 315–300 Ma have distinct metallogenic affinities typical for subduction-related rocks and are not found anywhere outside the Middle Tien Shan terrane west of the Talas–Farghona fault; (3) the Early Permian Hercynian post-collisional magmatism culminated after the closure of the Paleo-Turkestan ocean and affected the whole region across terrane boundaries. The post-collisional intrusions formed within a relatively short time span between 295 and 280 Ma. The model for Hercynian post-collisional evolution suggests that after collision the Tien Shan was affected by trans-crustal strike-slip motions which provided suitable conduits for ascending asthenospheric material and heat influx in the crust. This produced both granitoid magmas and hydrothermal fluid flow. As a result post-collisional intrusions and orogenic Au deposits, known in the region, formed coevally and were tectonically controlled; (4) between 240 and 220 Ma a Triassic thermal event affected the region resulting in resetting and growth of new zircon grains which is detected on a regional scale. Probably the influx of heat into the crust during the Triassic was tectonically focused and varied significantly in different terranes. In the region under investigation the Triassic thermal event was not accompanied by any significant magmatic activity. Thus, after cessation of Hercynian post-collisional magmatism ca. 280 Ma ago there was a long magmatically quiet period in the Tien Shan.

Time of Occurrence of Kidney Acute Antibody-Mediated Allograft Rejection/Acute Cellular Rejection and Cell Senescence: Implications for Function Outcome

Background Late versus early acute antibody-mediated rejection (AAMR) or acute cellular rejection (ACR) episodes are associated with poorer kidney function and graft survival. We explored whether cell senescence upon detection of AAMR ± ACR contributes to these results. Methods We reviewed the renal transplant database of 2 Institutions. Biopsies performed for acute graft dysfunction from January 2000 to March 2007 were analyzed for morphological criteria of AAMR with or without ACR (n = 17 from 17 patients). Immunoperoxidase staining for p16 INK4B was performed on the remaining paraffin-embedded tissue in 9 of 17 cases. The average number of positive cells/high power field (HPF) was calculated in every case. Cases with rejection were grouped according to the time of presentation: early (<3 months n = 8) versus late (>3 months; n = 9). Graft function was obtained using the Modification of Diet in Renal Disease (mDRD) glomerular filtration rate estimate (eGFR) before, during rejection, and at the last visit, to calculate ΔeGFR. Results Nuclear expression of p16 INK4B was 12.2 ± 11.3 cells/HPF in 4 of 8 biopsies performed at a median of 23 (range = 4–80) days (early AAMR ± ACR), and 59.8 ± 51.3 cells/HPF in 5 of 9 biopsies performed at a median of 1171 (range = 279–3210) days (late AAMR ± ACR). eGFR before rejection was 48.5 ± 7.6 mL/min, and 43.7 ± 4.3 mL/min for early and late rejection episodes, respectively ( P = not significant [NS]). ΔeGFR of 12.5 ± 25.9 mL/min (early rejection), and −13.7 ± −12.3 mL/min (late rejection), versus last follow-up visit ( P = .02) occurred at a median of 143.9 ± 94.1 and 69.6 ± 35.1 weeks after the rejection episodes, respectively. Conclusions Even though the number of biopsies analyzed for p16 INK4a was small, it was evident that the number of cells expressing this marker of senescence was higher among biopsy specimens obtained with late rejection episodes. This finding suggests the presence of injuries prior to the rejection episode. The significantly lower eGFR at last follow-up in the late rejection group may translate to a reduced capacity of the repair process to sustain nephron function.

Luxurious Dump: Wasted Buildings and the Landscape of Pure Suspension

The Costanera Center building in the financial district of Santiago sat half-finished for months, exposing concrete and reinforcement bars contrasting with the glass-faced skyscrapers surrounding it; a banner a the site read “Icon of Latin American development”. Once a symbol of Chile soaring copper driven economy, the stalled project became an emblem of its decline after work ground to a halt last year on what would be South America’s tallest building. Conditions of labour also deteriorated as this particular project started to crumble, and workers saw how their salaries – tied to timings and targets – were put at risk and their labour was literally wasted. This essay approaches the idea of the wasteland by looking at how this and other buildings in Chile have formed dumping grounds not of traditional waste but of half-finished structures, temporarily (or even permanently) useless forms of architecture; as dumping grounds, they have become void spaces within the city, places that people surround but not cross through, yet, paradoxically, they are very luxurious in terms of money spent and soil prices. The essay will approach the project reworking some of the ideas proposed by the artist Robert Smithson in his influential 1960s writings about the industrial wasteland of New Jersey; opposing the Romantic view of ruins, the artist proposes that these waste spaces do not fall into decay but rather rise into ruin before they are built; they are, he argues, ruins in reverse. Interestingly, Smithson links these spaces with his ideas about erosion, entropy and nature-made disasters, which also come together in the case of Chile and the devastation of its recent earthquake, a disaster that deepened the suspended state of some of its buildings. These constructions remain in a semi-permanent state of suspension, as a terrain of potentiality that could be, or not.

Service utilization patterns for presumed infertile women in the Islamic republic of Iran, 2004–2005

Understanding the utilization pattern of infertility health and medical services can assist health system managers in providing better and more efficient care to affected population. This study aims to investigate the patterns in the utilization of infertility services in Iran.We performed a survey of 10 783 women in 28 provinces from 2004 to 2005. We used a systematic sampling method to draw a total of 400 clusters, the probability for selection being proportional to the size of the urban and rural population in each province. The categorization of the woman as "presumed infertile" was based on her own report of infertility at some time during her married life. We also studied the measures taken for the latest episode of presumed infertility. For each of these measures, we recorded the reason(s), the year in which it was taken, and the time interval separating it from contraceptive discontinuation. Data analysis, using the software package STATA 8.0, included descriptive statistics and computation of 95% confidence intervals (CI) as well as chi(2) and logistic regression procedures adapted to the complex sampling design.A total of 1592 women had presumed infertility at some period after their marriage (14.8%, CI0.95 = 13.8-15.7%), and 1291 subjects had taken measures to deal with the problem (81.1%, CI0.95 = 78.7-83.5%). These rates did not show any significant differences between urban and rural women (p > 0.05). In 70% of these cases, the first measure was a visit to a specialist physician and in 70% the woman had sought care in the private sector. Visits to specialists and private health care facilities had increased over the last three decades, with fewer visits to general practitioners (GPs) and midwives and less use of self-medication or traditional/local therapies. The most common motive for those who had not taken any treatment was their unwillingness to have their problem known and discussed by others (29.3%). The determinants of treatment-seeking behavior were current primary infertility (OR = 4.15, CI0.95 = 2.53-6.80), higher education (OR = 1.39, CI0.95 = 1.04-1.86) and living with husband (OR = 1.83, CI0.95 = 1.01-3.32).The current study is the first attempt to present a population-based pattern of service utilization by infertile women in Iran. It shows that for these patients, the first contact with the health system takes the form of a visit to a specialist physician, and is more likely to involve the private sector.

No global-scale transgressive–regressive cycles in the Thanetian (Paleocene): Evidence from interregional correlation

A detailed examination of transgressions and regressions that occurred during the Thanetian (58.7–55.8 Ma) may provide an important constraint on the global palaeoenvironment. Seven tectonically “stable” regions (the eastern Russian Platform, Northwestern Europe, Northwestern Africa, Northeastern Africa, the Arabian Platform, the northern Gulf of Mexico, and Southern Australia), represent exceptional records of transgressive–regressive (T–R) cyclicity. Their chronostratigraphic frameworks are sufficiently well constrained to permit accurate correlation. Surprisingly, except for a generally regressive trend occurring in the late Thanetian, no common T–R cycles can be delineated, which indicates an absence of global-scale T–R cyclicity during the Thanetian. Furthermore, we find no clear correspondence between documented T–R patterns and previously reported eustatic changes. We suggest that a warm climate and an absence of major glaciations in the early-middle Thanetian, coupled with only slow eustatic change expected from tectonic processes, stabilized Thanetian eustatic sea level. Regional subsidence or uplift, possibly generated by mantle flow in the form of dynamic topography, governed transgressions and regressions locally and resulted in an inconsistency between T–R cycles in different parts of the globe. The late Thanetian regressive episode, which preceded the Paleocene–Eocene Thermal Maximum, may be linked to an advance of glaciation.

Long-term outcomes and quality of life after intestine transplantation

Over the past decade intestine transplantation has been accepted as standard therapy for patients with life-threatening complications of parenteral nutrition. For patients without life-threatening complications, continued therapy with parenteral nutrition has been standard despite seemingly similar patient survival in the short term. It is important to define the long-term patient and graft survival as well as complications encountered late after transplantation in order to understand the role for expansion of the indications for intestinal transplantation. Divergent immunosuppression strategies have been proposed by single centers, largely with similar improvements in patient survival over time. Current patient survival in the short term (1 year) and long term (5-10 years) have reached 78-85% and 56-61% in single-center series. Distinguishing the cause of diarrhea after the closure of the ostomy is problematic and justifies the ongoing efforts to identify a biomarker that might be used in place of allograft biopsy. Late rejection episodes are largely related to viral infections or noncompliance and the risk for malignancy appears confined primarily to adult recipients. Nutritional and growth parameters of children more than 2 years after intestinal transplantation demonstrate the majority have excellent bowel function/absorption (albeit frequent eating disorders) and normal growth velocity. Finally, preliminary reports from several new studies of quality of life after intestinal transplantation have been able to correlate the decreases in quality of life described to complications of the transplant or ongoing need for invasive devices or nutritional support. For patients who undergo intestinal transplantation patient survival appears similar to remaining on parenteral nutrition. The inclination is therefore to move toward earlier transplantation and avoid the need for concomitant liver transplantation. The long-term outcomes, however, are not thoroughly described and at this time it appears premature to electively offer intestinal transplantation.

Mechanisms of the Rapid Decline in Glomerular Filtration Rate following Lung Transplantation in Patients with Cystic Fibrosis

To the Editor:We read with interest the recent article by Hornum et al.on the rapid decline in renal function during the first weekspost lung transplantation (1). We fully agree that strategiesfor renoprotective regimens are required notably in thevulnerable peri- and postoperative period. It is important tohighlighttheadditionalaccelerateddeclineinrenalfunctionpost lung transplant in patients with cystic fibrosis (CF)when compared to non-CF lung transplantation recipients(2).The histopathological lesions differ in the early renal func-tion loss versus late stages post lung transplantation inpatients with CF. Calcineurin toxicity is important in the ac-celerated renal function decline post lung transplantation,however, the contribution of additional CF- associated fac-tors also deserve mention (3). The early accelerated renalfunction loss is thought to be additionally associated withoxalate nephropathy and pigmented tubulopathy; whereasthese factors are less important in late episodes of renalfunction loss (3).The etiology of oxalate nephropathy in CF patients is mul-tifactorial including: (1) Enteric Hyperoxaluria from the de-creaseincolonicOxalobacterformigenescolonizationsec-ondary to recurrent antibiotic usage in the treatment of CFpulmonary infective exacerbations, reduced gastrointesti-nal oxalate binding from dietary calcium deficiency andfatty acid malabsorption as a consequence of CF malab-sorption (2). Increased renal calcium oxalate deposition onthe surface of proximal tubular cells potentiated by periop-erative stressors including hemodynamic factors, hypoxia,antibiotics and other nephrotoxic agents. In this contextstrategies that reduce oxalate nephropathy in the peri- andpostoperative management of CF lung transplantation re-cipients have been suggested (4), including a reduction indietary oxalate, increased oral calcium supplementation,the avoidance of ascorbic acid (a precursor of oxalic acid),improving hydration status, judicious antibiotic use, poten-tial recolonization of the digestive tract with Oxalobacterformigenes and postoperative monitoring for crystalluriaand/or calcium oxalate supersaturation (4).Pigmented tubulopathy is characterized by the intracellularaccumulation of silver stain positive pigmented granuleswiththehistopathologicalcharacteristicsoflipofucsin.Thisoccurrence has been noted to correlate with antiviral ther-apy, aminoglycoside use and glycopeptides antibiotics inthe month preceding the accelerated renal function loss ina cohort of post lung transplant CF patients (3).Understandingthepathogenesisofacceleratedrenalfunc-tion loss specific to CF lung transplant recipients will facil-itate improved tailored strategies for preventing/retardingthe decline in glomerular filtration rates in this subgroup ofyour population.O. J. O’Connell

The Global Financial Crisis: How Similar? How Different? How Costly?

This paper provides a brief analysis of three major questions raised in the context of the recent global financial crisis. First, how similar is the crisis to previous episodes? We argue that the crisis featured some close similarities to earlier ones, including the presence of credit and asset price booms fueled by rapid debt accumulation. Second, how different is it from earlier episodes? We show that, as much as it displayed some similarities with previous cases, it also featured some significant differences, such as the explosion of opaque and complex financial instruments in a context of highly integrated global financial markets. Third, how costly are recessions that followed these types of crises? Although the latest episode took a very heavy toll on the real economy, we argue that this was not a surprising outcome. In particular, historical comparisons indicate that recessions associated with periods of deep financial disruptions result in much larger declines in real economic activity. We discuss the implications of these findings for economic and financial sector policies and future research.

The global financial crisis: How similar? How different? How costly?

This paper provides a brief analysis of three major questions raised in the context of the recent global financial crisis. First, how similar is the crisis to previous episodes? We argue that the crisis featured some close similarities to earlier ones, including the presence of credit and asset price booms fueled by rapid debt accumulation. Second, how different is it from earlier episodes? We show that, as much as it displayed some similarities with previous cases, it also featured some significant differences, such as the explosion of opaque and complex financial instruments in a context of highly integrated global financial markets. Third, how costly are recessions that followed these types of crises? Although the latest episode took a very heavy toll on the real economy, we argue that this was not a surprising outcome. In particular, historical comparisons indicate that recessions associated with periods of deep financial disruptions result in much larger declines in real economic activity. We discuss the implications of these findings for economic and financial sector policies and future research.