Use of Living Donors for Renal Homotransplantation

The procedure is described which is followed at the University of Colorado Medical Center for the selection and evaluation of living donors for renal homotransplantation. Priority is given to volunteers who have a close genetic relationship to the recipient. The aortogram is the single most useful test for determining which kidney to be used. If either organhas a single artery, it can be employed for homografting without fear of encountering anatomic difficulties at the time of its subsequent insertion into the recipient. Twenty-two left and 18 right kidneys have been excised. The donor operation has been a safe one. The only complications have been two pneumothoraces, one atelectasis, one transient peroneal nerve palsy, and two subcutaneous wound infections. Renal hyperplasia of the remaining kidney apparently occurs promptly since the creatinine clearance returns to or toward normal within a few weeks after operation. Interestingly, the same phenomenon is also observed in the homograft in those recipients who have a successful result. The steps in the donor operation are described for both right and left sides. Wide exposure, block removal of the specimen, and meticulous technique are required both to protect the donor from surgical accidents and to insure a homograft of high quality. Homograft cooling is provided eitherby total body hypothermia of the donor or by a method in which intra-arterial infusion of a chilled electrolyte solution isused. The relative future roles of living and cadaveric donors are discussed. The results with parental or sibling donations have been good enough to justify further employment of these sources. In cases in which a genetically unrelated donor must be used, a sounder policy may be to seek cadaveric organs, especially if the recipient falls in an older age group. © 1964 American Medical Association All rights reserved

Renal homografts in patients with major donor-recipient blood group incompatibilities

Three documented cases of clinical renal transplantation in which the donor and recipient patients had different major blood types have been presented. The relationship of the donor-recipient pairs ranged from that of sister-to-brother to that of totally unrelated patients of different races. The renal homografts were obtained from living donors in 2 cases and from a recently dead cadaver in the third. Renal function was prompt and excellent when living donors were used, and more indolent when a cadaver kidney subjected to a long period of ischemia was employed. Two of the patients have normal renal function after 74 and 49 days. The third patient died with rejection and sepsis 24 days after transplantation. This study demonstrates the feasibility of obtaining both immediate and prolonged renal function despite the presence of major blood group incompatibilities between donor and recipient patients. This knowledge should expand the donor pool, making it possible to transfer renal homografts under much less stringent requirements than has been the case in the past. © 1964

Temporal correlations in population trends: Conservation implications from time-series analysis of diverse animal taxa

Population trends play a large role in species risk assessments and conservation planning, and species are often considered threatened if their recent rate of decline meets certain thresholds, regardless how large the population is. But how reliable an indicator of extinction risk is a single estimate of population trend? Given the integral role this decline-based approach has played in setting conservation priorities, it is surprising that it has undergone little empirical scrutiny. We compile an extensive global dataset of time series of abundance data for over 1300 vertebrate populations to provide the first major test of the predictability of population growth rates in nature. We divided each time series into assessment and response periods and examined the correlation between growth rates in the two time periods. In birds, population declines tended to be followed by further declines, but mammals, salmon, and other bony fishes showed the opposite pattern: past declines were associated with subsequent population increases, and vice versa. Furthermore, in these taxa subsequent growth rates were higher when initial declines were more severe. These patterns agreed with data simulated under a null model for a dynamically stable population experiencing density dependence. However, this type of result could also occur if conservation actions positively affected the population following initial declines—a scenario that our data were too limited to rigorously evaluate. This ambiguity emphasizes the importance of understanding the underlying causes of population trajectories in drawing inferences about rates of decline in abundance

The IBER study: a feasibility randomised controlled trial of imagery based emotion regulation for the treatment of anxiety in bipolar disorder

BACKGROUND: Intrusive mental imagery is associated with anxiety and mood instability within bipolar disorder and therefore represents a novel treatment target. Imagery Based Emotion Regulation (IBER) is a brief structured psychological intervention developed to enable people to use the skills required to regulate the emotional impact of these images. METHODS: Participants aged 18 and over with a diagnosis of bipolar disorder and at least a mild level of anxiety were randomly assigned (1:1) to receive IBER plus treatment as usual (IBER + TAU) or treatment as usual alone (TAU). IBER was delivered in up to 12 sessions overs 16 weeks. Clinical and health economic data were collected at baseline, end of treatment and 16-weeks follow-up. Objectives were to inform the recruitment process, timeline and sample size estimate for a definitive trial and to refine trial procedures. We also explored the impact on participant outcomes of anxiety, depression, mania, and mood stability at 16-weeks and 32-weeks follow-up. RESULTS: Fifty-seven (28: IBER + TAU, 27: TAU) participants from two sites were randomised, with 50 being recruited within the first 12 months. Forty-seven (82%) participants provided outcome data at 16 and 32-weeks follow-up. Thirty-five participants engaged in daily mood monitoring at the 32-week follow-up stage. Retention in IBER treatment was high with 27 (96%) attending ≥ 7 sessions. No study participants experienced a serious adverse event. DISCUSSION: The feasibility criteria of recruitment, outcome completion, and intervention retention were broadly achieved, indicating that imagery-focused interventions for bipolar disorder are worthy of further investigation

Stroke genetics: prospects for personalized medicine.

Epidemiologic evidence supports a genetic predisposition to stroke. Recent advances, primarily using the genome-wide association study approach, are transforming what we know about the genetics of multifactorial stroke, and are identifying novel stroke genes. The current findings are consistent with different stroke subtypes having different genetic architecture. These discoveries may identify novel pathways involved in stroke pathogenesis, and suggest new treatment approaches. However, the already identified genetic variants explain only a small proportion of overall stroke risk, and therefore are not currently useful in predicting risk for the individual patient. Such risk prediction may become a reality as identification of a greater number of stroke risk variants that explain the majority of genetic risk proceeds, and perhaps when information on rare variants, identified by whole-genome sequencing, is also incorporated into risk algorithms. Pharmacogenomics may offer the potential for earlier implementation of 'personalized genetic' medicine. Genetic variants affecting clopidogrel and warfarin metabolism may identify non-responders and reduce side-effects, but these approaches have not yet been widely adopted in clinical practice

Paradoxical reversal learning enhancement by stress or prefrontal cortical damage: rescue with BDNF.

Stress affects various forms of cognition. We found that moderate stress enhanced late reversal learning in a mouse touchscreen-based choice task. Ventromedial prefrontal cortex (vmPFC) lesions mimicked the effect of stress, whereas orbitofrontal and dorsolateral striatal lesions impaired reversal. Stress facilitation of reversal was prevented by BDNF infusion into the vmPFC. These findings suggest a mechanism by which stress-induced vmPFC dysfunction disinhibits learning by alternate (for example, striatal) systems

The Thermal Design, Characterization, and Performance of the SPIDER Long-Duration Balloon Cryostat

We describe the SPIDER flight cryostat, which is designed to cool six millimeter-wavelength telescopes during an Antarctic long-duration balloon flight. The cryostat, one of the largest to have flown on a stratospheric payload, uses liquid helium-4 to deliver cooling power to stages at 4.2 and 1.6 K. Stainless steel capillaries facilitate a high flow impedance connection between the main liquid helium tank and a smaller superfluid tank, allowing the latter to operate at 1.6 K as long as there is liquid in the 4.2 K main tank. Each telescope houses a closed cycle helium-3 adsorption refrigerator that further cools the focal planes down to 300 mK. Liquid helium vapor from the main tank is routed through heat exchangers that cool radiation shields, providing negative thermal feedback. The system performed successfully during a 17 day flight in the 2014-2015 Antarctic summer. The cryostat had a total hold time of 16.8 days, with 15.9 days occurring during flight.Comment: 15 pgs, 17 fig

Testing for hereditary thrombophilia: a retrospective analysis of testing referred to a national laboratory

<p>Abstract</p> <p>Background</p> <p>Predisposition to venous thrombosis may be assessed through testing for defects and/or deficiencies of a number of hereditary factors. There is potential for confusion about which of these tests are appropriate in which settings. At least one set of recommendations has been published to guide such testing, but it is unclear how widely these have been disseminated.</p> <p>Methods</p> <p>We performed a retrospective analysis of laboratory orders and results at a national referral laboratory to gain insight into physicians' ordering practices, specifically comparing them against the ordering practices recommended by a 2002 College of American Pathologists (CAP) consensus conference on thrombophilia testing. Measurements included absolute and relative ordering volumes and positivity rates from approximately 200,000 thrombophilia tests performed from September 2005 through August 2006 at a national reference laboratory. Quality control data were used to estimate the proportion of samples that may have been affected by anticoagulant therapy. A sample of ordering laboratories was surveyed in order to assess potential measurement bias.</p> <p>Results</p> <p>Total antigen assays for protein C, protein S and antithrombin were ordered almost as frequently as functional assays for these analytes. The DNA test for factor V Leiden was ordered much more often than the corresponding functional assay. In addition, relative positivity rates coupled with elevations in prothrombin time (PT) in many of these patients suggest that these tests are often ordered in the setting of oral anticoagulant therapy.</p> <p>Conclusion</p> <p>In this real-world setting, testing for inherited thrombophilia is frequently at odds with the recommendations of the CAP consensus conference. There is a need for wider dissemination of concise thrombophilia testing guidelines.</p

Actin and myosin contribute to mammalian mitochondrial DNA maintenance.

Mitochondrial DNA maintenance and segregation are dependent on the actin cytoskeleton in budding yeast. We found two cytoskeletal proteins among six proteins tightly associated with rat liver mitochondrial DNA: non-muscle myosin heavy chain IIA and β-actin. In human cells, transient gene silencing of MYH9 (encoding non-muscle myosin heavy chain IIA), or the closely related MYH10 gene (encoding non-muscle myosin heavy chain IIB), altered the topology and increased the copy number of mitochondrial DNA; and the latter effect was enhanced when both genes were targeted simultaneously. In contrast, genetic ablation of non-muscle myosin IIB was associated with a 60% decrease in mitochondrial DNA copy number in mouse embryonic fibroblasts, compared to control cells. Gene silencing of β-actin also affected mitochondrial DNA copy number and organization. Protease-protection experiments and iodixanol gradient analysis suggest some β-actin and non-muscle myosin heavy chain IIA reside within human mitochondria and confirm that they are associated with mitochondrial DNA. Collectively, these results strongly implicate the actomyosin cytoskeleton in mammalian mitochondrial DNA maintenance.Medical Research Council; the European Union; the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development and National Heart; Lung and Blood Institute; National Institutes of Health and grants [CMRPG360491-2, 380651, NSC 97-2321-B-182A-002-MY2] from the Chang Gung Memorial Hospital, Lin-Kou, Taiwan (to C.C.M.). Funding for open access charge: Medical Research Council