Low Dopamine D2/D3 Receptor Availability is Associated with Steep Discounting of Delayed Rewards in Methamphetamine Dependence.

BackgroundIndividuals with substance use disorders typically exhibit a predilection toward instant gratification with apparent disregard for the future consequences of their actions. Indirect evidence suggests that low dopamine D2-type receptor availability in the striatum contributes to the propensity of these individuals to sacrifice long-term goals for short-term gain; however, this possibility has not been tested directly. We investigated whether striatal D2/D3 receptor availability is negatively correlated with the preference for smaller, more immediate rewards over larger, delayed alternatives among research participants who met DSM-IV criteria for methamphetamine (MA) dependence.MethodsFifty-four adults (n = 27 each: MA-dependent, non-user controls) completed the Kirby Monetary Choice Questionnaire, and underwent positron emission tomography scanning with [(18)F]fallypride.ResultsMA users displayed steeper temporal discounting (p = 0.030) and lower striatal D2/D3 receptor availability (p < 0.0005) than controls. Discount rate was negatively correlated with striatal D2/D3 receptor availability, with the relationship reaching statistical significance in the combined sample (r = -0.291, p = 0.016) and among MA users alone (r = -0.342, p = 0.041), but not among controls alone (r = -0.179, p = 0.185); the slopes did not differ significantly between MA users and controls (p = 0.5).ConclusionsThese results provide the first direct evidence of a link between deficient D2/D3 receptor availability and steep temporal discounting. This finding fits with reports that low striatal D2/D3 receptor availability is associated with a higher risk of relapse among stimulant users, and may help to explain why some individuals choose to continue using drugs despite knowledge of their eventual negative consequences. Future research directions and therapeutic implications are discussed

Management of the Acute Scrotum in a District General Hospital: 10-Year Experience

The acutely painful scrotum is a common urologic emergency. The primary objective of management is to avoid testicular loss. This requires a high index of clinical suspicion and prompt surgical intervention. In our series conducted between January 1996 and December 2005, 119 patients (age range: 4–62 years) underwent emergency operative exploration for acute scrotal pain. The most common finding was torted cyst of Morgagni (63/119, 52.9%), followed by testicular torsion (41/119, 34.4%). The majority of testicular torsions occurred in the pubertal group (22/41, 53.6%). Only one patient in this group had an unsalvageable testis necessitating orchidectomy, a testicular loss rate in torsion of 2.4%. There were no postoperative wound infections or scrotal haematomas. Testicular salvage depends critically on early surgical intervention, so the delay incurred in diagnostic imaging may extend the period of ischaemia. Furthermore, all radiological investigations have a certain false-negative rate. We advocate immediate surgical exploration of the acute scrotum. We report a low orchidectomy rate (2.4%) in testicular torsion

Maintenance hemodialysis patients have high cumulative radiation exposure

Hemodialysis is associated with an increased risk of neoplasms which may result, at least in part, from exposure to ionizing radiation associated with frequent radiographic procedures. In order to estimate the average radiation exposure of those on hemodialysis, we conducted a retrospective study of 100 patients in a university-based dialysis unit followed for a median of 3.4 years. The number and type of radiological procedures were obtained from a central radiology database, and the cumulative effective radiation dose was calculated using standardized, procedure-specific radiation levels. The median annual radiation dose was 6.9 millisieverts (mSv) per patient-year. However, 14 patients had an annual cumulative effective radiation dose over 20mSv, the upper averaged annual limit for occupational exposure. The median total cumulative effective radiation dose per patient over the study period was 21.7mSv, in which 13 patients had a total cumulative effective radiation dose over 75mSv, a value reported to be associated with a 7% increased risk of cancer-related mortality. Two-thirds of the total cumulative effective radiation dose was due to CT scanning. The average radiation exposure was significantly associated with the cause of end-stage renal disease, history of ischemic heart disease, transplant waitlist status, number of in-patient hospital days over follow-up, and death during the study period. These results highlight the substantial exposure to ionizing radiation in hemodialysis patients

Advanced Colloids Experiment (Temperature Controlled) ACE-T5

The attached will be presented at the JSC Science Symposium as a preview of the ACE-T5 flight experiment. The Principal Investigator (PI) for this experiment is Professor Ali Mohraz at the University of California - Irvine.Bijels (bicontinuous interfacially jammed emulsion gels) were discovered in 2007 at the University of Edinburgh. These materials feature a tubular, bicontinuous arrangement of two fluid phases separated by a monolayer of jammed colloidal particles at the interface.Because of their unique morphological characteristics, bijels hold significant promise as next-generation materials for energy and biotechnology applications. But in order to fully realize their potential, their physics and mechanical properties must be better understood. The mechanical properties and stability of bijels is mediated by an interplay between interfacial forces that impart elasticity to the system, and external stresses. Unfortunately, the interfacial forces are inherently coupled with density differences and cannot be studied systematically in the presence of gravity

Mycophenolate mofetil treatment for primary glomerular diseases

Mycophenolate mofetil treatment for primary glomerular diseases.BackgroundTreatment of primary glomerular diseases may be unsuccessful or have potential toxicities. Therefore, we evaluated the use of mycophenolate mofetil (MMF) for empirical treatment of primary glomerulopathies.MethodsForty-six patients with biopsy-proven primary glomerulopathies received MMF for ≥3 months as adjunctive or primary treatment. Median (range) 24-hour urine protein to creatinine ratio (Up/c) and serum creatinine at the start and end of MMF therapy were compared using the Wilcoxon signed-ranks test.ResultsOverall, the median Up/c decreased from 4.7 (range <0.1, 20.3) to 1.1 (<0.1, 14.3; P < 0.001) at the end of MMF treatment with no significant change in median serum creatinine 1.3 (0.6 to 6.1) to 1.2 (0.5 to 6.5) mg/dL. Median serum albumin increased from 3.4 (1.4, 4.6) to 4.1 (1.7, 48) g/dL (P < 0.001) and the median serum cholesterol decreased from 270 (148, 795) to 220 (140, 309) mg/dL (P < 0.001) post-treatment. For those with minimal change disease, a complete steroid withdrawal was accomplished in 5/6 steroid dependent patients. Focal segmental glomerulosclerosis (FSGS) patients had a median Up/c that decreased from 2.7 (0.1, 20.3) to 0.8 (<0.1, 8.2; P = 0.001) in 18 patients. In membranous nephropathy (MN) patients, the median Up/c decreased from 7.3 (0.1, 18.5) to 1.5 (<0.1, 14.3) (P = 0.001) in 17 patients. No significant change in median serum creatinine was detected in FSGS or MN patient groups during treatment.ConclusionsEmpirical MMF therapy in the majority of patients with primary glomerulopathies was well tolerated and achieved the goals of steroid withdrawal, improvement of nephrotic syndrome, and stabilization of renal function

The Penicillin for the Emergency Department Outpatient treatment of CELLulitis (PEDOCELL) trial: update to the study protocol and detailed statistical analysis plan (SAP)

Background: Cellulitis is a painful, potentially serious, infectious process of the dermal and subdermal tissues and represents a significant disease burden. The statistical analysis plan (SAP) for the Penicillin for the Emergency Department Outpatient treatment of CELLulitis (PEDOCELL) trial is described here. The PEDOCELL trial is a multicentre, randomised, parallel-arm, double-blinded, non-inferiority clinical trial comparing the efficacy of flucloxacillin (monotherapy) with combination flucloxacillin/phenoxymethylpenicillin (dual therapy) for the outpatient treatment of cellulitis in the emergency department (ED) setting. To prevent outcome reporting bias, selective reporting and data-driven results, the a priori-defined, detailed SAP is presented here. Methods/design: Patients will be randomised to either orally administered flucloxacillin 500 mg four times daily and placebo or orally administered 500 mg of flucloxacillin four times daily and phenoxymethylpenicillin 500 mg four times daily. The trial consists of a 7-day intervention period and a 2-week follow-up period. Study measurements will be taken at four specific time points: at patient enrolment, day 2-3 after enrolment and commencing treatment (early clinical response (ECR) visit), day 8-10 after enrolment (end-of-treatment (EOT) visit) and day 14-21 after enrolment (test-of-cure (TOC) visit). The primary outcome measure is investigator-determined clinical response measured at the TOC visit. The secondary outcomes are as follows: lesion size at ECR, clinical treatment failure at each follow-up visit, adherence and persistence of trial patients with orally administered antibiotic therapy at EOT, health-related quality of life (HRQoL) and pharmacoeconomic assessments. The plan for the presentation and comparison of baseline characteristics and outcomes is described in this paper. Discussion: This trial aims to establish the non-inferiority of orally administered flucloxacillin monotherapy with orally administered flucloxacillin/phenoxymethylpenicillin dual therapy for the ED-directed outpatient treatment of cellulitis. In doing so, this trial will bridge a knowledge gap in this understudied and common condition and will be relevant to clinicians across several different disciplines. The SAP for the PEDOCELL trial was developed a priori in order to minimise analysis bias

Culture-independent analyses reveal novel Anaerolineaceae as abundant primary fermenters in anaerobic digesters treating waste activated sludge:Genomic insights into the A6 phylotype

Anaerobic digestion for biogas production is reliant on the tightly coupled synergistic activities of complex microbial consortia. Members of the uncultured A6 phylotype, within the phylum Chloroflexi, are among the most abundant genus-level-taxa of mesophilic anaerobic digester systems treating primary and surplus sludge from wastewater treatment plants, yet are known only by their 16S rRNA gene sequence. This study applied metagenomics to obtain a complete circular genome (2.57 Mbp) from a representative of the A6 taxon. Preliminary annotation of the genome indicates these organisms to be anaerobic chemoorganoheterotrophs with a fermentative metabolism. Given their observed abundance, they are likely important primary fermenters in digester systems. Application of fluorescence in situ hybridisation probes designed in this study revealed their morphology to be short filaments present within the flocs. The A6 were sometimes co-located with the filamentous Archaea Methanosaeta spp. suggesting potential undetermined synergistic relationships. Based on its genome sequence and morphology we propose the species name Brevefilum fermentans gen. nov. sp. nov

Advanced Colloids Experiment (Temperature Controlled) - ACE-T12

Increment 57-58 Science Symposium presentation of Advanced Colloids Experiment (ACE-T12) to RPO. The purpose of this event is for Principal Investigators to present their science objectives, testing approach, and measurement methods to agency scientists, managers, and other investigators. This flight experiment was added after the Science Symposium, so these charts for more for reference, than presentation

Radiologic imaging in cystic fibrosis: cumulative effective dose and changing trends over 2 decades

Objective: With the increasing life expectancy for patients with cystic fibrosis (CF), and a known predisposition to certain cancers, cumulative radiation exposure from radiologic imaging is of increasing significance. This study explores the estimated cumulative effective radiation dose over a 17-year period from radiologic procedures and changing trends of imaging modalities over this period. Methods: Estimated cumulative effective dose (CED) from all thoracic and extrathoracic imaging modalities and interventional radiology procedures for both adult and pediatric patients with CF, exclusively attending a nationally designated CF center between 1992-2009 for > 1 year, was determined. The study period was divided into three equal tertiles, and estimated CED attributable to all radiologic procedures was estimated for each tertile. Results: Two hundred thirty patients met inclusion criteria (2,240 person-years of follow-up; 5,596 radiologic procedures). CED was > 75 mSv for one patient (0.43%), 36 patients (15.6%) had a CED between 20 and 75 mSv, 56 patients (24.3%) had a CED between 5 and 20 mSv, and in 138 patients (60%) the CED was estimated to be between 0 and 5 mSv over the study period. The mean annual CED per patient increased consecutively from 0.39 mSv/y to 0.47 mSv/y to 1.67 mSv/y over the tertiles one to three of the study period, respectively (P < .001). Thoracic imaging accounted for 46.9% of the total CED and abdominopelvic imaging accounted for 42.9% of the CED, respectively. There was an associated 5.9-fold increase in the use of all CT scanning per patient (P < .001). Conclusions: This study highlights the increasing exposure to ionizing radiation to patients with CF as a result of diagnostic imaging, primarily attributable to CT scanning. Increased awareness of CED and strategies to reduce this exposure are needed